AmberMDFlow for HF Space (no binaries)

Co-authored-by: Cursor <cursoragent@cursor.com>

.dockerignore

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+# Git
+.git
+.gitignore
+
+# Python
+__pycache__
+*.pyc
+*.pyo
+*.pyd
+.Python
+*.so
+*.egg
+*.egg-info
+dist
+build
+.pytest_cache
+.coverage
+htmlcov
+
+# Virtual environments
+venv/
+env/
+ENV/
+
+# IDE
+.vscode/
+.idea/
+*.swp
+*.swo
+*~
+
+# OS
+.DS_Store
+Thumbs.db
+
+# Output and temporary files
+output/
+temp/
+*.log
+*.tmp
+
+# Documentation
+*.md
+!README.md
+
+# Docker
+Dockerfile
+docker-compose.yml
+.dockerignore
+
+# Other
+*.bak
+*.backup
+

.gitattributes

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+*.7z filter=lfs diff=lfs merge=lfs -text
+*.arrow filter=lfs diff=lfs merge=lfs -text
+*.bin filter=lfs diff=lfs merge=lfs -text
+*.bz2 filter=lfs diff=lfs merge=lfs -text
+*.ckpt filter=lfs diff=lfs merge=lfs -text
+*.ftz filter=lfs diff=lfs merge=lfs -text
+*.gz filter=lfs diff=lfs merge=lfs -text
+*.h5 filter=lfs diff=lfs merge=lfs -text
+*.joblib filter=lfs diff=lfs merge=lfs -text
+*.lfs.* filter=lfs diff=lfs merge=lfs -text
+*.mlmodel filter=lfs diff=lfs merge=lfs -text
+*.model filter=lfs diff=lfs merge=lfs -text
+*.msgpack filter=lfs diff=lfs merge=lfs -text
+*.npy filter=lfs diff=lfs merge=lfs -text
+*.npz filter=lfs diff=lfs merge=lfs -text
+*.onnx filter=lfs diff=lfs merge=lfs -text
+*.ot filter=lfs diff=lfs merge=lfs -text
+*.parquet filter=lfs diff=lfs merge=lfs -text
+*.pb filter=lfs diff=lfs merge=lfs -text
+*.pickle filter=lfs diff=lfs merge=lfs -text
+*.pkl filter=lfs diff=lfs merge=lfs -text
+*.pt filter=lfs diff=lfs merge=lfs -text
+*.pth filter=lfs diff=lfs merge=lfs -text
+*.rar filter=lfs diff=lfs merge=lfs -text
+*.safetensors filter=lfs diff=lfs merge=lfs -text
+saved_model/**/* filter=lfs diff=lfs merge=lfs -text
+*.tar.* filter=lfs diff=lfs merge=lfs -text
+*.tar filter=lfs diff=lfs merge=lfs -text
+*.tflite filter=lfs diff=lfs merge=lfs -text
+*.tgz filter=lfs diff=lfs merge=lfs -text
+*.wasm filter=lfs diff=lfs merge=lfs -text
+*.xz filter=lfs diff=lfs merge=lfs -text
+*.zip filter=lfs diff=lfs merge=lfs -text
+*.zst filter=lfs diff=lfs merge=lfs -text
+*tfevents* filter=lfs diff=lfs merge=lfs -text

.gitignore

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+# Python
+__pycache__/
+*.py[cod]
+*$py.class
+*.so
+.Python
+build/
+develop-eggs/
+dist/
+downloads/
+eggs/
+.eggs/
+lib/
+lib64/
+parts/
+sdist/
+var/
+wheels/
+*.egg-info/
+.installed.cfg
+*.egg
+
+# Virtual environments
+venv/
+env/
+ENV/
+
+# IDE
+.vscode/
+.idea/
+*.swp
+*.swo
+
+# OS
+.DS_Store
+Thumbs.db
+
+# Project specific
+output/
+*.log
+*.tmp
+temp/
+
+# PDB files (optional - remove if you want to include example PDBs)
+*.pdb
+*.ent
+
+# AMBER files
+*.prmtop
+*.inpcrd
+*.rst
+*.rst7
+*.ncrst
+*.mdcrd
+*.nc
+*.dcd
+*.xtc
+*.trr
+
+# Binaries (HF Spaces rejects; logo can be hosted elsewhere)
+AmberMDFlow.png

Dockerfile

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+FROM python:3.9-slim
+
+# Install system dependencies
+RUN apt-get update && apt-get install -y \
+    wget \
+    curl \
+    build-essential \
+    gcc \
+    g++ \
+    make \
+    libffi-dev \
+    libssl-dev \
+    libglib2.0-0 \
+    libxext6 \
+    libsm6 \
+    libxrender1 \
+    libgomp1 \
+    && rm -rf /var/lib/apt/lists/*
+
+# Install Miniforge (conda-forge–based; no Anaconda ToS) and configure channels
+RUN wget -q https://github.com/conda-forge/miniforge/releases/latest/download/Miniforge3-Linux-x86_64.sh && \
+    bash Miniforge3-Linux-x86_64.sh -b -p /opt/conda && \
+    rm Miniforge3-Linux-x86_64.sh
+
+ENV PATH="/opt/conda/bin:${PATH}"
+
+# Add bioconda; conda-forge is default for Miniforge. No Anaconda ToS needed.
+RUN conda config --add channels bioconda && \
+    conda config --set channel_priority flexible
+
+# Install mamba for faster package installation
+RUN conda install -n base -c conda-forge mamba -y
+
+# Install AMBER tools, PyMOL, AutoDock Vina 1.1.2, Open Babel, RDKit, and gemmi (for Meeko)
+RUN mamba install -y python=3.11 \
+    conda-forge::ambertools conda-forge::pymol-open-source \
+    bioconda::autodock-vina conda-forge::openbabel conda-forge::rdkit conda-forge::gemmi
+
+# Clean up conda/mamba cache to reduce image size
+RUN conda clean -afy
+
+# Install Python packages via pip (only packages not provided by conda or that need pip)
+# Note: numpy, pandas, matplotlib are already installed by conda; don't override to avoid conflicts
+RUN pip install --no-cache-dir \
+    flask==2.3.3 \
+    flask-cors==4.0.0 \
+    biopython \
+    seaborn \
+    mdanalysis \
+    gunicorn==21.2.0 \
+    requests \
+    meeko>=0.7.0 \
+    prody \
+    "numpy<2.0"
+
+# Set working directory
+WORKDIR /AmberMDFlow
+
+# Copy the entire project
+COPY . .
+
+# Create necessary directories with proper permissions
+RUN mkdir -p /AmberMDFlow/obsolete /AmberMDFlow/pdb /AmberMDFlow/temp /AmberMDFlow/output && \
+    chmod -R 777 /AmberMDFlow
+
+# Make sure the ambermdflow package is on the Python path
+ENV PYTHONPATH="${PYTHONPATH}:/AmberMDFlow"
+
+# Expose the port
+EXPOSE 7860
+
+# Run the application
+CMD ["python", "start_web_server.py"]
+

LICENSE

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+MIT License
+
+Copyright (c) 2025 Hemant Nagar
+
+Permission is hereby granted, free of charge, to any person obtaining a copy
+of this software and associated documentation files (the "Software"), to deal
+in the Software without restriction, including without limitation the rights
+to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
+copies of the Software, and to permit persons to whom the Software is
+furnished to do so, subject to the following conditions:
+
+The above copyright notice and this permission notice shall be included in all
+copies or substantial portions of the Software.
+
+THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
+IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
+FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
+AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
+LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
+OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
+SOFTWARE.

MANIFEST.in

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+# Include package data
+recursive-include ambermdflow/html *
+recursive-include ambermdflow/css *
+recursive-include ambermdflow/js *
+
+# Include documentation
+include README.md
+include LICENSE
+
+# Exclude development/test files
+exclude .gitignore
+exclude .dockerignore
+exclude Dockerfile
+prune Test
+prune __pycache__
+global-exclude *.pyc
+global-exclude *.pyo
+global-exclude .DS_Store

README.md

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+---
+title: AmberMDFlow
+sdk: docker
+app_port: 7860
+---
+
+# AmberMDFlow
+
+**AmberMDFlow** is a web-based pipeline for preparing structures, setting up molecular dynamics (MD) simulations with the AMBER force field. It integrates structure completion (ESMFold), preparation, force field parameterization, simulation file generation, and PLUMED-based biased MD in a single interface. This is the beta version.
+
+---
+
+## Note
+- If you plan to dock ligands and have filled missing residues in the protein chain using ESMFold, you should also energy-minimize the structure.
+- The **Fill Missing Residues** option works only for PDB files retrieved from the RCSB database, as it relies on the REMARK 465 records to identify missing residues.
+- The public ESMFold API is used to predict protein structures from input sequences, and it supports sequences of up to 400 amino acids.
+
+---
+
+## Features
+
+| Section | Description |
+|--------|-------------|
+| **Protein Loading** | Upload PDB files or fetch from RCSB PDB; 3D visualization with NGL |
+| **Fill Missing Residues** | Detect missing residues (RCSB annotations), complete with ESMFold, optional trimming and energy minimization of predicted structure|
+| **Structure Preparation** | Remove water/ions/H; add ACE/NME capping; chain and ligand selection; GAFF/GAFF2 parameterization |
+| **Ligand Docking** | AutoDock Vina + Meeko; configurable search box; pose selection and use selected ligand pose to setup MD simulations |
+| **Simulation Parameters** | Force fields (ff14SB, ff19SB), water models (TIP3P, SPCE), box size, temperature, pressure |
+| **Simulation Steps** | Restrained minimization, minimization, NVT, NPT, production — each with configurable parameters |
+| **Generate Files** | AMBER `.in` files, `prmtop`/`inpcrd`, PBS submission scripts |
+| **PLUMED** | Collective variables (PLUMED v2.9), `plumed.dat` editor, and simulation file generation with PLUMED |
+
+---
+
+## Requirements for Custom PDB Files
+
+For **custom PDB files** (uploaded or fetched), ensure:
+
+| Requirement | Description |
+|-------------|-------------|
+| **Chain IDs** | Chain IDs (A,B,C..) must be clearly marked in the PDB file. |
+| **Ligands as HETATM** | All ligands must be in **HETATM** records with name and IDs marked (LIG and A). |
+| **Standard amino acids** | AmberMDFlow supports **standard amino acids** only. Non-standard residues and residues with PTMs are currently not supported in the pipeline. |
+
+For RCSB structures, the pipeline parses the header and HETATM as provided; for your own PDBs, apply the above conventions.
+
+---
+
+## Quick Start
+
+Try AmberMDFlow instantly on Hugging Face Spaces (no installation required):
+
+**[https://huggingface.co/spaces/hemantn/AmberMDFlow](https://huggingface.co/spaces/hemantn/AmberMDFlow)**
+
+---
+
+## Installation
+
+### Prerequisites
+
+AmberMDFlow requires scientific packages that are only available via **conda** (not PyPI). You must install these first:
+
+| Package | Purpose |
+|---------|---------|
+| `ambertools` | AMBER MD tools (tleap, antechamber, sander) |
+| `pymol-open-source` | Structure visualization and editing |
+| `autodock-vina` | AutoDock Vina 1.1.2 molecular docking (from bioconda) |
+| `openbabel` | Molecule format conversion |
+| `rdkit` | Cheminformatics toolkit |
+| `gemmi` | Structure file parsing (required by Meeko) |
+
+---
+
+### Option 1: pip install (recommended)
+
+```bash
+# Step 1: Create conda environment with required tools
+conda create -n ambermdflow python=3.11 -y
+conda activate ambermdflow
+
+# Step 2: Install conda-only dependencies
+conda install -c conda-forge -c bioconda ambertools pymol-open-source autodock-vina openbabel rdkit gemmi -y
+
+# Step 3: Install AmberMDFlow from Test PyPI
+pip install --extra-index-url https://test.pypi.org/simple/ ambermdflow
+
+# Step 4: Run the web app
+ambermdflow
+```
+
+Open your browser at **http://localhost:7860**
+
+---
+
+### Option 2: Docker (no conda/pip needed)
+**build from source:**
+```bash
+git clone https://github.com/nagarh/AmberMDFlow.git
+cd AmberMDFlow
+docker build -t ambermdflow .
+docker run -p 7860:7860 ambermdflow
+```
+
+Open your browser at **http://localhost:7860**
+
+---
+
+### Troubleshooting
+
+| Issue | Solution |
+|-------|----------|
+| `ModuleNotFoundError: No module named 'gemmi'` | Run: `conda install -c conda-forge gemmi` |
+| `vina: command not found` | Run: `conda install -c conda-forge vina` |
+| Port 7860 already in use | Kill the process or edit `start_web_server.py` to use a different port |
+
+
+---
+
+## Usage
+
+### 1. Protein Loading
+
+- **Upload**: Drag-and-drop or choose a `.pdb` file.
+- **Fetch**: Enter a 4-character PDB ID (e.g. `1HPV`) to download from RCSB.
+
+After loading, the **Protein Preview** shows: structure ID, atom count, chains, residues, water, ions, ligands, and HETATM count. Use the 3D viewer to inspect the structure.
+
+---
+
+### 2. Fill Missing Residues
+
+- Click **Analyze Missing Residues** to detect gaps from RCSB metadata.
+- **Select chains** to complete with ESMFold.
+- **Trim residues** (optional): remove residues from N- or C-terminal edges; internal loops are always filled by ESMFold.
+- **Energy minimization** (optional): if you enable ESMFold completion, you can minimize selected chains to resolve clashes before docking. Recommended if receptor preparation (Meeko) fails later.
+- **Build Completed Structure** to run ESMFold and (if requested) minimization. Use **Preview Completed Structure** and **View Superimposed Structures** to compare original and completed chains.
+
+> If you use ESMFold in this workflow, please cite [ESM Atlas](https://esmatlas.com/about).
+
+---
+
+### 3. Structure Preparation
+
+- **Remove**: Water, ions, and hydrogens (options are pre-configured).
+- **Add capping**: ACE (N-terminal) and NME (C-terminal).
+- **Chains**: Select which protein chains to keep for force field generation.
+- **Ligands**:
+  - **Preserve ligands** to keep them in the structure.
+  - **Select ligands to preserve** (e.g. `GOL-A-1`, `LIZ-A`). Unselected ligands are dropped.
+  - **Create separate ligand file** to export selected ligand(s) to a PDB.
+  - **Protonate** ligand using Open Babel.
+
+Click **Prepare Structure**. The status panel reports original vs prepared atom counts, removed components, added capping, and preserved ligands. Use **View Prepared Structure** and **Download Prepared PDB** as needed.
+
+**Ligand Docking** (nested in this tab):
+
+- Select ligands to dock.
+- Set the **search space** (center and size in X, Y, Z) with live 3D visualization.
+- **Run Docking** (AutoDock Vina + Meeko). Progress and logs are shown in the docking panel.
+- **Select poses** per ligand and **Use selected pose** to write the chosen pose into the structure for AMBER. You can switch modes (e.g. 1–9) and jump by clicking the mode labels.
+
+---
+
+### 4. Simulation Parameters
+
+- **Force field**: ff14SB or ff19SB.
+- **Water model**: TIP3P or SPCE.
+- **Box size** (Å): padding for solvation.
+- **Add ions**: to neutralize (and optionally reach a salt concentration).
+- **Temperature** and **Pressure** (e.g. 300 K, 1 bar).
+- **Time step** and **Cutoff** for non-bonded interactions.
+
+If ligands were preserved, **Ligand force field** (GAFF/GAFF2) is configured here; net charge is computed before `antechamber` runs.
+
+---
+
+### 5. Simulation Steps
+
+Enable/disable and set parameters for:
+
+- **Restrained minimization** (steps, force constant)
+- **Minimization** (steps, cutoff)
+- **NVT heating** (steps, temperature)
+- **NPT equilibration** (steps, temperature, pressure)
+- **Production** (steps, temperature, pressure)
+
+---
+
+### 6. Generate Files
+
+- **Generate All Files** to create AMBER inputs (`min_restrained.in`, `min.in`, `HeatNPT.in`, `mdin_equi.in`, `mdin_prod.in`), `tleap` scripts, `submit_job.pbs`, and (after `tleap`) `prmtop`/`inpcrd`.
+- **Preview Files** to open and **edit** each file (e.g. `min.in`, `submit_job.pbs`) and **Save**; changes are written to the output directory.
+- **Preview Solvated Protein** / **Download Solvated Protein** to inspect and download the solvated system.
+
+For **PLUMED-based runs**, go to the **PLUMED** tab to configure CVs and `plumed.dat`, then use **Generate simulation files** there to produce inputs that include PLUMED.
+
+---
+
+### 7. PLUMED
+
+- **Collective Variables**: search and select CVs from the PLUMED v2.9 set; view docs and add/edit lines in `plumed.dat`.
+- **Custom PLUMED**: edit `plumed.dat` directly.
+- **Generate simulation files**: create AMBER + PLUMED input files. Generated files can be **previewed, edited, and saved** as in the main **Generate Files** tab.
+
+> PLUMED citation: [plumed.org/cite](https://www.plumed.org/cite).
+
+---
+
+## Pipeline Overview
+
+```
+Protein Loading (upload/fetch)
+        ↓
+Fill Missing Residues (detect → ESMFold → optional trim & minimize)
+        ↓
+Structure Preparation (clean, cap, chains, ligands) → optional Docking (Vina, select pose)
+        ↓
+Simulation Parameters (FF, water, box, T, P, etc.)
+        ↓
+Simulation Steps (min, NVT, NPT, prod)
+        ↓
+Generate Files (AMBER .in, tleap, prmtop/inpcrd, PBS)
+        ↓
+[Optional] PLUMED (CVs, plumed.dat, generate PLUMED-enabled files)
+```
+
+---
+
+## Output Layout
+
+Generated files are written under `output/` (or the path set in the app), for example:
+
+- `0_original_input.pdb` — raw input
+- `1_protein_no_hydrogens.pdb` — cleaned, capped, chain/ligand selection applied
+- `2_protein_with_caps.pdb`, `tleap_ready.pdb` — intermediates
+- `4_ligands_corrected_*.pdb` — prepared ligands
+- `protein.prmtop`, `protein.inpcrd` — after `tleap`
+- `min_restrained.in`, `min.in`, `HeatNPT.in`, `mdin_equi.in`, `mdin_prod.in`, `submit_job.pbs`
+- `output/docking/` — receptor, ligands, Vina configs, poses, logs
+- `plumed.dat` — when using PLUMED
+
+---
+
+## Multi-user deployment (e.g. Hugging Face Spaces)
+
+When multiple users use the app at the same time (e.g. on Hugging Face Spaces), each user gets an **isolated output folder** so one user’s files are not overwritten by another’s. The app assigns a session ID when the page loads; all API requests send this ID and generated files are stored under `output/<session_id>/`. No configuration is required—this works automatically in multi-user and single-user setups.
+
+---
+
+## Dependencies
+
+| Category | Tools / libraries |
+|----------|-------------------|
+| **Python** | Flask, Flask-CORS, BioPython, NumPy, Pandas, Matplotlib, Seaborn, MDAnalysis, Requests, RDKit, SciPy |
+| **AMBER** | AMBER Tools (tleap, antechamber, sander, ambpdb, etc.) |
+| **Docking** | Meeko (`mk_prepare_ligand`, `mk_prepare_receptor`), AutoDock Vina, Open Babel |
+| **Visualization** | PyMOL (scripted for H removal, structure editing), NGL (in-browser 3D) |
+| **Structure completion** | ESMFold (via API or local, depending on deployment) |
+
+---
+
+## Project Structure
+
+```
+AmberMDFlow/
+├── start_web_server.py      # Entry point
+├── html/
+│   ├── index.html           # Main UI
+│   └── plumed.html          # PLUMED-focused view (if used)
+├── css/
+│   ├── styles.css
+│   └── plumed.css
+├── js/
+│   ├── script.js            # Main frontend logic
+│   ├── plumed.js            # PLUMED + docking UI
+│   └── plumed_cv_docs.js    # CV documentation
+├── python/
+│   ├── app.py               # Flask backend, API, file generation
+│   ├── structure_preparation.py
+│   ├── add_caps.py          # ACE/NME capping
+│   ├── Fill_missing_residues.py  # ESMFold, trimming, minimization
+│   ├── docking.py           # Docking helpers
+│   └── docking_utils.py
+├── output/                  # Generated files (gitignored in dev)
+├── Dockerfile
+└── README.md
+```
+
+---
+
+## Citation
+
+If you use AmberMDFlow in your work, please cite:
+
+```bibtex
+@software{AmberMDFlow,
+  title = {AmberMDFlow: Molecular Dynamics and Docking Pipeline},
+  author = {Nagar, Hemant},
+  year = {2025},
+  url = {https://github.com/nagarh/AmberMDFlow}
+```
+
+**Related software to cite when used:**
+
+- **AMBER**: [ambermd.org](https://ambermd.org)
+- **PLUMED**: [plumed.org/cite](https://www.plumed.org/cite)
+- **ESMFold / ESM Atlas**: [esmatlas.com/about](https://esmatlas.com/about)
+- **AutoDock Vina**: [autodock-vina/cite](https://autodock-vina.readthedocs.io/en/latest/citations.html)
+- **Meeko**: [github.com/forlilab/Meeko](https://github.com/forlilab/Meeko)
+- **MDAnalysis**: [mdanalysis/cite](https://www.mdanalysis.org/pages/citations/)
+- **NGL Viewer**: [nglviewer/cite](https://doi.org/10.1093/bioinformatics/bty419)
+- **PyMOL**: [pymol/cite](https://www.pymol.org/support.html) 
+
+---
+
+## Acknowledgments
+
+- **Mohd Ibrahim** (Technical University of Munich) for the protein capping logic (`add_caps.py`).
+
+---
+
+## License
+
+MIT License. See `LICENSE` for details.
+
+---
+
+## Contact
+
+- **Author**: Hemant Nagar  
+- **Email**: hn533621@ohio.edu

ambermdflow/Fill_missing_residues.py

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+import requests
+from collections import defaultdict
+from textwrap import wrap
+import re
+
+
+def get_pdb_id_from_pdb_file(pdb_path):
+    """
+    Extract the 4-character PDB ID from a PDB file.
+
+    By convention, PDB files have a line starting with 'HEADER' where
+    columns 63–66 contain the PDB ID code.
+
+    If that cannot be found, this function will raise a ValueError so
+    that the pipeline fails loudly instead of silently doing the wrong thing.
+    """
+    with open(pdb_path, "r") as fh:
+        for line in fh:
+            if line.startswith("HEADER") and len(line) >= 66:
+                pdb_id = line[62:66].strip()
+                if pdb_id:
+                    return pdb_id.upper()
+
+    raise ValueError(
+        f"Could not determine PDB ID from file: {pdb_path}. "
+        "Expected a 'HEADER' record with ID in columns 63–66."
+    )
+
+GRAPHQL_URL = "https://data.rcsb.org/graphql"
+
+def detect_missing_residues(pdb_id):
+    url = f"https://files.rcsb.org/download/{pdb_id}.pdb"
+    response = requests.get(url)
+    response.raise_for_status()
+
+    missing_by_chain = defaultdict(list)
+
+    for line in response.text.splitlines():
+        if line.startswith("REMARK 465"):
+            parts = line.split()
+            if len(parts) >= 5 and parts[2].isalpha():
+                resname = parts[2]
+                chain = parts[3]
+
+                # Extract residue number (strip insertion code, handle negative numbers)
+                match = re.match(r"(-?\d+)", parts[4])
+                if match:
+                    resnum = int(match.group(1))
+                    missing_by_chain[chain].append((resname, resnum))
+
+    return dict(missing_by_chain)
+
+def get_chain_sequences(pdb_id):
+    query = """
+    query ChainSequences($pdb_id: String!) {
+      entry(entry_id: $pdb_id) {
+        polymer_entities {
+          entity_poly {
+            pdbx_seq_one_letter_code_can
+          }
+          polymer_entity_instances {
+            rcsb_polymer_entity_instance_container_identifiers {
+              auth_asym_id
+            }
+          }
+        }
+      }
+    }
+    """
+
+    r = requests.post(
+        GRAPHQL_URL,
+        json={"query": query, "variables": {"pdb_id": pdb_id}}
+    )
+    r.raise_for_status()
+
+    chain_seqs = {}
+
+    for entity in r.json()["data"]["entry"]["polymer_entities"]:
+        seq = entity["entity_poly"]["pdbx_seq_one_letter_code_can"]
+        for inst in entity["polymer_entity_instances"]:
+            chain = inst[
+                "rcsb_polymer_entity_instance_container_identifiers"
+            ]["auth_asym_id"]
+            chain_seqs[chain] = seq
+
+    return chain_seqs
+
+def trim_residues_from_edges(sequence, n_terminal_trim=0, c_terminal_trim=0):
+    """
+    Trim residues from the edges (N-terminal and C-terminal) of a sequence.
+    Only trims from the edges, not from loops in between.
+    
+    Args:
+        sequence: str
+            The amino acid sequence to trim
+        n_terminal_trim: int
+            Number of residues to remove from the N-terminal (start)
+        c_terminal_trim: int
+            Number of residues to remove from the C-terminal (end)
+    
+    Returns:
+        str: The trimmed sequence
+    
+    Raises:
+        ValueError: If trim counts exceed sequence length or are negative
+    """
+    if n_terminal_trim < 0 or c_terminal_trim < 0:
+        raise ValueError("Trim counts must be non-negative")
+    
+    if n_terminal_trim + c_terminal_trim >= len(sequence):
+        raise ValueError(
+            f"Total trim count ({n_terminal_trim + c_terminal_trim}) exceeds sequence length ({len(sequence)})"
+        )
+    
+    # Trim from N-terminal (start) and C-terminal (end)
+    trimmed = sequence[n_terminal_trim:len(sequence) - c_terminal_trim]
+    
+    return trimmed
+
+
+def trim_chains_sequences(chains_with_sequences, trim_specs):
+    """
+    Apply trimming to multiple chain sequences based on specifications.
+    
+    Args:
+        chains_with_sequences: dict
+            Dictionary mapping chain IDs to sequences
+            Example: {'A': 'MKTAYIAKQR...', 'B': 'MKTAYIAKQR...'}
+        trim_specs: dict
+            Dictionary mapping chain IDs to trim specifications
+            Each specification is a dict with 'n_terminal' and/or 'c_terminal' keys
+            Example: {'A': {'n_terminal': 5, 'c_terminal': 3}, 'B': {'n_terminal': 2}}
+    
+    Returns:
+        dict: Dictionary mapping chain IDs to trimmed sequences
+    """
+    trimmed_chains = {}
+    
+    for chain, sequence in chains_with_sequences.items():
+        if chain in trim_specs:
+            spec = trim_specs[chain]
+            n_term = spec.get('n_terminal', 0)
+            c_term = spec.get('c_terminal', 0)
+            
+            try:
+                trimmed_seq = trim_residues_from_edges(sequence, n_term, c_term)
+                trimmed_chains[chain] = trimmed_seq
+            except ValueError as e:
+                raise ValueError(f"Error trimming chain {chain}: {str(e)}")
+        else:
+            # No trimming specified for this chain, keep original
+            trimmed_chains[chain] = sequence
+    
+    return trimmed_chains
+
+
+def write_fasta_for_missing_chains(pdb_id, chains_with_missing, output_dir=None):
+    """
+    Write FASTA file for chains with missing residues.
+    
+    Args:
+        pdb_id: PDB identifier
+        chains_with_missing: Dictionary mapping chain IDs to sequences
+        output_dir: Optional output directory. If None, writes to current directory.
+    """
+    filename = f"{pdb_id}_chains_with_missing.fasta"
+    
+    if output_dir:
+        from pathlib import Path
+        output_path = Path(output_dir) / filename
+    else:
+        output_path = filename
+
+    with open(output_path, "w") as f:
+        for chain, seq in chains_with_missing.items():
+            f.write(f">{pdb_id.upper()}_{chain}\n")
+            for line in wrap(seq, 60):
+                f.write(line + "\n")
+
+    print(f"Wrote FASTA: {output_path}")
+
+def run_esmfold(sequence):
+    response = requests.post(
+        "https://api.esmatlas.com/foldSequence/v1/pdb/",
+        data=sequence,
+        timeout=300
+    )
+    response.raise_for_status()
+    return response.text
+
+
+def merge_non_protein_atoms(original_pdb_path, protein_pdb_path, output_pdb_path, chains_to_replace):
+    """
+    Add non-protein atoms (water, ions, ligands) from original file to the completed protein structure.
+    
+    Parameters:
+    -----------
+    original_pdb_path : str
+        Path to the original PDB file
+    protein_pdb_path : str
+        Path to the temporary protein-only PDB file
+    output_pdb_path : str
+        Path where the final merged PDB will be written
+    chains_to_replace : list[str]
+        List of chain IDs that were replaced by ESMFold (not used, kept for compatibility)
+    """
+    import os
+    
+    # Extract non-protein atoms (HETATM records) from original PDB
+    non_protein_atoms = []
+    
+    if not os.path.exists(original_pdb_path):
+        print(f"Warning: Original PDB file not found: {original_pdb_path}")
+        # Just copy the protein file if original doesn't exist
+        if os.path.exists(protein_pdb_path):
+            import shutil
+            shutil.copy2(protein_pdb_path, output_pdb_path)
+        return
+    
+    # Read HETATM records from original PDB
+    with open(original_pdb_path, 'r') as f:
+        for line in f:
+            if line.startswith('HETATM'):
+                # Include all HETATM records (water, ions, ligands)
+                non_protein_atoms.append(line)
+    
+    # Read the completed protein structure
+    if not os.path.exists(protein_pdb_path):
+        print(f"Error: Protein PDB file not found: {protein_pdb_path}")
+        return
+    
+    # Write merged PDB file: protein structure + non-protein atoms
+    with open(output_pdb_path, 'w') as f:
+        # Write the completed protein structure (all lines except END)
+        with open(protein_pdb_path, 'r') as protein_file:
+            for line in protein_file:
+                if not line.startswith('END'):
+                    f.write(line)
+        
+        # Add non-protein atoms (water, ions, ligands) from original
+        for line in non_protein_atoms:
+            f.write(line)
+        
+        # Write END record at the very end
+        f.write("END                                                                             \n")
+    
+    print(f"✅ Added {len(non_protein_atoms)} non-protein atoms to completed structure")
+
+
+def rebuild_pdb_with_esmfold(
+    pdb_id,
+    chains_to_replace,
+    output_pdb=None,
+    original_pdb_path=None,
+    chains_use_minimized=None,
+):
+    """
+    pdb_id: str
+        Original crystal structure object name (e.g. '3hhr')
+
+    chains_to_replace: list[str]
+        Chains that were missing residues and replaced by ESMFold
+        Example: ['A', 'B', 'C']
+
+    output_pdb: str, optional
+        Output PDB filename.
+
+    original_pdb_path: str, optional
+        Path to the original PDB file that should be loaded into PyMOL
+        as the reference object named `pdb_id`. If None, defaults to
+        '../../output/0_original_input.pdb'.
+
+    chains_use_minimized: list[str], optional
+        For these chains, load the superimposed minimized PDB
+        ({pdb_id}_chain_{c}_esmfold_minimized_noH.pdb) instead of the
+        ESMFold PDB. The minimized structure is aligned to the original
+        the same way as ESMFold (CA-based superimposition).
+    """
+
+    from pymol import cmd
+
+    # -----------------------------
+    # 0. Clean up any existing objects with the same names
+    # -----------------------------
+    try:
+        # Delete existing objects if they exist
+        existing_objects = cmd.get_object_list()
+        if pdb_id in existing_objects:
+            cmd.delete(pdb_id)
+        
+        # Delete any existing ESMFold objects for the chains we're processing
+        for chain in chains_to_replace:
+            esm_obj = f"{pdb_id}_chain_{chain}_esmfold"
+            if esm_obj in existing_objects:
+                cmd.delete(esm_obj)
+        
+        # Delete final_model if it exists
+        if "final_model" in existing_objects:
+            cmd.delete("final_model")
+    except Exception as e:
+        print(f"Warning: Could not clean up existing objects: {e}")
+
+    # -----------------------------
+    # 1. Load original PDB into PyMOL
+    # -----------------------------
+    if original_pdb_path is None:
+        # Default to the pipeline output location
+        original_pdb_path = "../../output/0_original_input.pdb"
+
+    print(f"Loading original PDB from {original_pdb_path} as object '{pdb_id}'")
+    cmd.load(original_pdb_path, pdb_id)
+
+    if output_pdb is None:
+        output_pdb = f"{pdb_id}_rebuilt.pdb"
+
+    # -----------------------------
+    # 2. Align each ESMFold (or minimized) chain and fix chain IDs
+    # -----------------------------
+    for chain in chains_to_replace:
+        esm_obj = f"{pdb_id}_chain_{chain}_esmfold"
+
+        # For minimized chains, use the superimposed minimized noH PDB
+        # (minimization writes in a different frame; we align it to original here).
+        if chains_use_minimized and chain in chains_use_minimized:
+            esm_pdb_filename = f"{pdb_id}_chain_{chain}_esmfold_minimized_noH.pdb"
+            print(f"Loading minimized PDB {esm_pdb_filename} as object '{esm_obj}' (will superimpose to original)")
+        else:
+            esm_pdb_filename = f"{pdb_id}_chain_{chain}_esmfold.pdb"
+            print(f"Loading ESMFold PDB {esm_pdb_filename} as object '{esm_obj}'")
+        cmd.load(esm_pdb_filename, esm_obj)
+
+        # ESMFold outputs everything as chain A by default.
+        # Rename the chain in the loaded object to match the target chain ID.
+        print(f"Renaming chain A -> {chain} in {esm_obj}")
+        cmd.alter(esm_obj, f"chain='{chain}'")
+        cmd.sort(esm_obj)  # Rebuild internal indices after alter
+
+        align_cmd = (
+            f"{esm_obj} and name CA",
+            f"{pdb_id} and chain {chain} and name CA"
+        )
+
+        print(f"Aligning {esm_obj} to {pdb_id} chain {chain}")
+        cmd.align(*align_cmd)
+
+    # -----------------------------
+    # 3. Build selection strings
+    # -----------------------------
+    chains_str = "+".join(chains_to_replace)
+
+    esm_objs_str = " or ".join(
+        f"{pdb_id}_chain_{chain}_esmfold"
+        for chain in chains_to_replace
+    )
+
+    selection = (
+        f"({pdb_id} and not chain {chains_str}) or "
+        f"({esm_objs_str})"
+    )
+
+    # -----------------------------
+    # 4. Create final model
+    # -----------------------------
+    cmd.select("final_model", selection)
+
+    # -----------------------------
+    # 5. Save rebuilt structure (protein only)
+    # -----------------------------
+    import os
+    temp_protein_pdb = output_pdb.replace('.pdb', '_protein_temp.pdb')
+    cmd.save(temp_protein_pdb, "final_model")
+    
+    # -----------------------------
+    # 6. Add non-protein atoms from original PDB
+    # -----------------------------
+    print(f"Adding non-protein atoms from original file...")
+    # Convert paths to absolute paths if they're relative
+    abs_original = os.path.abspath(original_pdb_path) if original_pdb_path else None
+    abs_temp = os.path.abspath(temp_protein_pdb)
+    abs_output = os.path.abspath(output_pdb)
+    merge_non_protein_atoms(abs_original, abs_temp, abs_output, chains_to_replace)
+    
+    # Clean up temporary protein file
+    try:
+        if os.path.exists(temp_protein_pdb):
+            os.remove(temp_protein_pdb)
+    except Exception as e:
+        print(f"Warning: Could not remove temporary file {temp_protein_pdb}: {e}")
+    
+    # -----------------------------
+    # 7. Clean up temporary objects (keep final_model for potential reuse)
+    # -----------------------------
+    try:
+        # Delete the original and ESMFold objects, but keep final_model
+        cmd.delete(pdb_id)
+        for chain in chains_to_replace:
+            esm_obj = f"{pdb_id}_chain_{chain}_esmfold"
+            cmd.delete(esm_obj)
+    except Exception as e:
+        print(f"Warning: Could not clean up temporary objects: {e}")
+
+    print(f"✅ Final rebuilt structure saved as: {output_pdb}")
+
+
+if __name__ == "__main__":
+    # Path to the original input PDB used by the pipeline
+    original_pdb_path = "../../output/0_original_input.pdb"
+
+    # Automatically infer the PDB ID from the original PDB file,
+    # instead of hard-coding it (e.g., '3hhr').
+    pdb_id = get_pdb_id_from_pdb_file(original_pdb_path)
+    print(f"Detected PDB ID from original file: {pdb_id}")
+
+    # 1) Find missing residues for this structure
+    missing = detect_missing_residues(pdb_id)
+    chain_sequences = get_chain_sequences(pdb_id)
+
+    chains_with_missing = {
+        chain: chain_sequences[chain]
+        for chain in missing
+        if chain in chain_sequences
+    }
+
+    # 2) Write FASTA for chains with missing residues
+    write_fasta_for_missing_chains(pdb_id, chains_with_missing)
+
+    # 3) Run ESMFold for each chain and save results
+    esmfold_results = {}
+    chains_to_replace = []
+
+    for chain, seq in chains_with_missing.items():
+        print(f"Running ESMFold for chain {chain}")
+        pdb_text = run_esmfold(seq)
+        esmfold_results[chain] = pdb_text
+        chains_to_replace.append(chain)
+        # Save each chain
+        with open(f"{pdb_id}_chain_{chain}_esmfold.pdb", "w") as f:
+            f.write(pdb_text)
+
+    # 4) Rebuild PDB in PyMOL using original structure and ESMFold chains
+    rebuild_pdb_with_esmfold(
+        pdb_id,
+        chains_to_replace,
+        original_pdb_path=original_pdb_path,
+    )

ambermdflow/__init__.py

@@ -0,0 +1,37 @@
+"""
+AmberMDFlow: Web-based MD simulation pipeline with AMBER, ESMFold, docking, and PLUMED.
+
+AmberMDFlow provides a complete workflow for:
+- Protein structure loading and visualization
+- Missing residue completion with ESMFold
+- Structure preparation (cleaning, capping, chain/ligand selection)
+- Ligand docking with AutoDock Vina + Meeko
+- AMBER force field parameterization
+- MD simulation file generation
+- PLUMED collective variable configuration
+
+Usage:
+    # Run the web interface
+    $ ambermdflow
+    # or
+    $ python -m ambermdflow
+
+    # Import in Python
+    from ambermdflow.app import app
+    from ambermdflow.structure_preparation import prepare_structure
+
+Requirements:
+    - Python >= 3.10
+    - Conda packages: ambertools, pymol-open-source, vina, openbabel, rdkit, gemmi
+    - See README.md for full installation instructions
+
+License: MIT
+"""
+
+__version__ = "0.0.1"
+__author__ = "Hemant Nagar"
+__email__ = "hn533621@ohio.edu"
+# Expose key components for programmatic use
+from ambermdflow.app import app
+
+__all__ = ["app", "__version__"]

ambermdflow/__main__.py

@@ -0,0 +1,11 @@
+"""Run the AmberMDFlow web server. Use: python -m ambermdflow or ambermdflow"""
+
+from ambermdflow.app import app
+
+
+def main():
+    app.run(debug=False, host="0.0.0.0", port=7860)
+
+
+if __name__ == "__main__":
+    main()

ambermdflow/add_caps.py

@@ -0,0 +1,176 @@
+# Written by Mohd Ibrahim
+# Technical University of Munich
+# Email: ibrahim.mohd@tum.de
+
+import numpy as np
+import MDAnalysis as mda
+import argparse
+import warnings
+warnings.filterwarnings("ignore")
+
+np.random.seed(42)  
+
+parser = argparse.ArgumentParser(
+    description="Add capping groups ACE and NME to protein termini. "
+                "Remove hydrogens before using this script")
+parser.add_argument('-i', dest='in_file', type=str,
+                    default='protein_noh.pdb', help='pdb file')
+parser.add_argument('-o', dest='out_file', type=str,
+                    default='protein_noh_cap.pdb', help='output file')
+
+args = parser.parse_args()
+in_file = args.in_file
+out_file = args.out_file
+
+
+def create_universe(n_atoms, name, resname, positions, resids, segid):
+    u_new = mda.Universe.empty(
+        n_atoms=n_atoms,
+        n_residues=n_atoms,
+        atom_resindex=np.arange(n_atoms),
+        residue_segindex=np.arange(n_atoms),
+        n_segments=n_atoms,
+        trajectory=True
+    )
+    u_new.add_TopologyAttr('name', name)
+    u_new.add_TopologyAttr('resid', resids)
+    u_new.add_TopologyAttr('resname', resname)
+    u_new.atoms.positions = positions
+    u_new.add_TopologyAttr('segid', n_atoms * [segid])
+    u_new.add_TopologyAttr('chainID', n_atoms * [segid])
+    return u_new
+
+
+def get_nme_pos(end_residue):
+    if "OXT" in end_residue.names:
+        index = np.where(end_residue.names == "OXT")[0][0]
+        N_position = end_residue.positions[index]
+        index_c = np.where(end_residue.names == "C")[0][0]
+        carbon_position = end_residue.positions[index_c]
+        vector = N_position - carbon_position
+        vector /= np.sqrt(sum(vector**2))
+        C_position = N_position + vector * 1.36
+        return N_position, C_position
+    else:
+        index_o = np.where(end_residue.names == "O")[0][0]
+        index_ca = np.where(end_residue.names == "CA")[0][0]
+        mid_point = (end_residue.positions[index_o] +
+                     end_residue.positions[index_ca]) / 2
+        index_c = np.where(end_residue.names == "C")[0][0]
+        vector = end_residue.positions[index_c] - mid_point
+        vector /= np.sqrt(sum(vector**2))
+        N_position = end_residue.positions[index_c] + 1.36 * vector
+        C_position = N_position + 1.36 * vector
+        return N_position, C_position
+
+
+def get_ace_pos(end_residue):
+    index_ca = np.where(end_residue.names == "CA")[0][0]
+    index_n = np.where(end_residue.names == "N")[0][0]
+    vector = end_residue.positions[index_n] - end_residue.positions[index_ca]
+    vector /= np.sqrt(sum(vector**2))
+    C1_position = end_residue.positions[index_n] + 1.36 * vector
+
+    xa, ya, za = end_residue.positions[index_ca]
+    xg, yg, zg = C1_position
+
+    orientation = np.array([2 * np.random.rand() - 1,
+                            2 * np.random.rand() - 1,
+                            2 * np.random.rand() - 1])
+    nx, ny, nz = orientation / np.sqrt(sum(orientation**2))
+
+    x1 = xg - (xa - xg) / 2 + np.sqrt(3) * (ny * (za - zg) - nz * (ya - yg)) / 2
+    y1 = yg - (ya - yg) / 2 + np.sqrt(3) * (nz * (xa - xg) - nx * (za - zg)) / 2
+    z1 = zg - (za - zg) / 2 + np.sqrt(3) * (nx * (ya - yg) - ny * (xa - xg)) / 2
+
+    x2 = xg - (xa - xg) / 2 - np.sqrt(3) * (ny * (za - zg) - nz * (ya - yg)) / 2
+    y2 = yg - (ya - yg) / 2 - np.sqrt(3) * (nz * (xa - xg) - nx * (za - zg)) / 2
+    z2 = zg - (za - zg) / 2 - np.sqrt(3) * (nx * (ya - yg) - ny * (xa - xg)) / 2
+
+    C2_position = np.array([x1, y1, z1])
+    O_position = np.array([x2, y2, z2])
+
+    vector = C2_position - C1_position
+    vector /= np.sqrt(sum(vector**2))
+    C2_position = C1_position + 1.36 * vector
+
+    vector = O_position - C1_position
+    vector /= np.sqrt(sum(vector**2))
+    O_position = C1_position + 1.36 * vector
+
+    return C1_position, C2_position, O_position
+
+
+# ----------- Main processing -----------
+u = mda.Universe(in_file)
+res_start = 0
+segment_universes = []
+
+for seg in u.segments:
+    chain = u.select_atoms(f"segid {seg.segid}")
+
+    # ACE
+    resid_c = chain.residues.resids[0]
+    end_residue = u.select_atoms(f"segid {seg.segid} and resid {resid_c}")
+    c1_pos, c2_pos, o_pos = get_ace_pos(end_residue)
+
+    # keep original mapping (C, CH3, O)
+    ace_names = ["C", "CH3", "O"]
+    ace_positions = [c1_pos, c2_pos, o_pos]
+    resid = chain.residues.resids[0]
+    ace_universe = create_universe(
+        n_atoms=len(ace_positions),
+        name=ace_names,
+        resname=len(ace_names) * ["ACE"],
+        positions=ace_positions,
+        resids=resid * np.ones(len(ace_names)),
+        segid=chain.segids[0]
+    )
+
+    # >>> Reorder rows only: CH3, C, O <<<
+    ace_universe = mda.Merge(
+        ace_universe.atoms.select_atoms("name CH3"),
+        ace_universe.atoms.select_atoms("name C"),
+        ace_universe.atoms.select_atoms("name O")
+    )
+
+    # NME
+    resid_c = chain.residues.resids[-1]
+    end_residue = u.select_atoms(f"segid {seg.segid} and resid {resid_c}")
+    nme_positions = get_nme_pos(end_residue)
+    nme_names = ["N", "C"]
+    resid = chain.residues.resids[-1] + 2
+    nme_universe = create_universe(
+        n_atoms=len(nme_names),
+        name=nme_names,
+        resname=len(nme_names) * ["NME"],
+        positions=nme_positions,
+        resids=resid * np.ones(len(nme_names)),
+        segid=chain.segids[0]
+    )
+
+    # Remove OXT if present
+    if "OXT" in end_residue.names:
+        index = np.where(end_residue.names == "OXT")[0][0]
+        OXT = end_residue[index]
+        Chain = u.select_atoms(f"segid {seg.segid} and not index {OXT.index}")
+    else:
+        Chain = u.select_atoms(f"segid {seg.segid}")
+
+    # Merge ACE, protein, NME
+    u_all = mda.Merge(ace_universe.atoms, Chain, nme_universe.atoms)
+
+    # Renumber residues
+    resids_ace = [res_start + 1] * 3
+    resids_pro = np.arange(resids_ace[0] + 1,
+                           Chain.residues.n_residues + resids_ace[0] + 1)
+    resids_nme = [resids_pro[-1] + 1] * 2
+    u_all.atoms.residues.resids = np.concatenate(
+        [resids_ace, resids_pro, resids_nme]
+    )
+    res_start = u_all.atoms.residues.resids[-1]
+    segment_universes.append(u_all)
+
+# Join and write output
+all_uni = mda.Merge(*(seg.atoms for seg in segment_universes))
+all_uni.atoms.write(out_file)

ambermdflow/css/plumed.css

@@ -0,0 +1,1064 @@
+/* PLUMED Section Styles */
+
+/* PLUMED Citation Note */
+.plumed-citation-note {
+    background: #e3f2fd;
+    border: 2px solid #2196f3;
+    border-left: 5px solid #2196f3;
+    border-radius: 8px;
+    padding: 1rem 1.5rem;
+    margin-bottom: 1.5rem;
+    display: flex;
+    align-items: flex-start;
+    gap: 1rem;
+    box-shadow: 0 2px 4px rgba(33, 150, 243, 0.1);
+}
+
+.plumed-citation-note i {
+    color: #2196f3;
+    font-size: 1.5rem;
+    margin-top: 0.2rem;
+    flex-shrink: 0;
+}
+
+.citation-content {
+    flex: 1;
+    color: #1565c0;
+    line-height: 1.6;
+}
+
+.citation-content p {
+    margin: 0.5rem 0;
+    font-size: 0.95rem;
+}
+
+.citation-content p:first-child {
+    margin-top: 0;
+}
+
+.citation-content p:last-child {
+    margin-bottom: 0;
+}
+
+.citation-content strong {
+    color: #0d47a1;
+    font-weight: 600;
+}
+
+.citation-content a {
+    color: #1976d2;
+    text-decoration: none;
+    font-weight: 500;
+    transition: color 0.3s ease;
+    display: inline-flex;
+    align-items: center;
+    gap: 0.25rem;
+}
+
+.citation-content a:hover {
+    color: #0d47a1;
+    text-decoration: underline;
+}
+
+.citation-content a i {
+    font-size: 0.85rem;
+    color: inherit;
+    margin: 0;
+}
+
+.plumed-container {
+    display: flex;
+    gap: 2rem;
+    margin-top: 1.5rem;
+    min-height: 600px;
+}
+
+/* Left Sidebar */
+.plumed-sidebar {
+    width: 300px;
+    background: #f8f9fa;
+    border-radius: 8px;
+    border: 1px solid #dee2e6;
+    display: flex;
+    flex-direction: column;
+    max-height: 800px;
+    overflow: hidden;
+}
+
+.sidebar-header {
+    padding: 1rem;
+    background: #2c3e50;
+    color: white;
+    border-bottom: 2px solid #3498db;
+}
+
+.sidebar-header h3 {
+    margin: 0 0 1rem 0;
+    font-size: 1.2rem;
+    font-weight: 600;
+}
+
+.sidebar-header h3 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+.search-box {
+    position: relative;
+}
+
+.search-input {
+    width: 100%;
+    padding: 0.5rem 2.5rem 0.5rem 0.75rem;
+    border: 1px solid #dee2e6;
+    border-radius: 4px;
+    font-size: 0.9rem;
+    transition: all 0.3s ease;
+}
+
+.search-input:focus {
+    outline: none;
+    border-color: #3498db;
+    box-shadow: 0 0 0 3px rgba(52, 152, 219, 0.1);
+}
+
+.search-icon {
+    position: absolute;
+    right: 0.75rem;
+    top: 50%;
+    transform: translateY(-50%);
+    color: #7f8c8d;
+    pointer-events: none;
+}
+
+.cv-list {
+    flex: 1;
+    overflow-y: auto;
+    padding: 0.5rem;
+}
+
+.cv-item {
+    padding: 0.75rem 1rem;
+    margin-bottom: 0.5rem;
+    background: white;
+    border: 1px solid #dee2e6;
+    border-radius: 6px;
+    cursor: pointer;
+    transition: all 0.3s ease;
+    display: flex;
+    align-items: center;
+    justify-content: space-between;
+}
+
+.cv-item:hover {
+    background: #e3f2fd;
+    border-color: #3498db;
+    transform: translateX(5px);
+}
+
+.cv-item.active {
+    background: #3498db;
+    color: white;
+    border-color: #2980b9;
+    box-shadow: 0 2px 8px rgba(52, 152, 219, 0.3);
+}
+
+.cv-item-name {
+    font-weight: 600;
+    font-size: 0.95rem;
+}
+
+.cv-item-category {
+    font-size: 0.75rem;
+    opacity: 0.7;
+    margin-top: 0.25rem;
+}
+
+.cv-item.active .cv-item-category {
+    opacity: 0.9;
+}
+
+.cv-item-icon {
+    color: #3498db;
+    margin-left: 0.5rem;
+}
+
+.cv-item.active .cv-item-icon {
+    color: white;
+}
+
+/* Right Content Panel */
+.plumed-content {
+    flex: 1;
+    background: white;
+    border-radius: 8px;
+    border: 1px solid #dee2e6;
+    padding: 1.5rem;
+    overflow-y: auto;
+    max-height: 800px;
+}
+
+.content-header {
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    margin-bottom: 1.5rem;
+    padding-bottom: 1rem;
+    border-bottom: 2px solid #e1e8ed;
+}
+
+.content-header h3 {
+    margin: 0;
+    color: #2c3e50;
+    font-size: 1.5rem;
+    display: flex;
+    align-items: center;
+    gap: 0.5rem;
+}
+
+.plumed-doc-link {
+    color: #3498db;
+    text-decoration: none;
+    font-size: 0.85em;
+    margin-left: 0.5rem;
+    transition: color 0.3s ease;
+    display: inline-flex;
+    align-items: center;
+    gap: 0.25rem;
+}
+
+.plumed-doc-link:hover {
+    color: #2980b9;
+    text-decoration: underline;
+}
+
+.plumed-doc-link i {
+    font-size: 0.75em;
+}
+
+.welcome-message {
+    text-align: center;
+    padding: 3rem 1rem;
+    color: #7f8c8d;
+}
+
+.welcome-message i {
+    color: #bdc3c7;
+    margin-bottom: 1rem;
+}
+
+.welcome-message h3 {
+    color: #2c3e50;
+    margin: 1rem 0;
+}
+
+/* Documentation Sections */
+.cv-documentation {
+    margin-bottom: 2rem;
+}
+
+.doc-section {
+    margin-bottom: 2rem;
+    padding: 1.5rem;
+    background: #f8f9fa;
+    border-radius: 8px;
+    border-left: 4px solid #3498db;
+}
+
+.doc-section h4 {
+    color: #2c3e50;
+    margin-bottom: 1rem;
+    font-size: 1.2rem;
+    display: flex;
+    align-items: center;
+}
+
+.doc-section h4 {
+    display: flex;
+    align-items: center;
+    margin-bottom: 1rem;
+}
+
+.doc-section h4 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+/* Options heading with legend on the right - only apply space-between to headings with color-legend */
+.doc-section h4 .color-legend {
+    margin-left: auto;
+}
+
+/* For browsers that support :has() */
+@supports selector(:has(*)) {
+    .doc-section h4:has(.color-legend) {
+        justify-content: space-between;
+        flex-wrap: wrap;
+        gap: 1rem;
+    }
+}
+
+/* Fallback for browsers without :has() support - use a class */
+.doc-section h4.options-heading-with-legend {
+    justify-content: space-between;
+    flex-wrap: wrap;
+    gap: 1rem;
+}
+
+.color-legend {
+    display: flex;
+    align-items: center;
+    gap: 1rem;
+    font-size: 0.85rem;
+    font-weight: normal;
+    color: #7f8c8d;
+    margin-left: auto;
+}
+
+.legend-item {
+    display: flex;
+    align-items: center;
+    gap: 0.5rem;
+}
+
+.legend-item code {
+    font-size: 0.8rem;
+    padding: 0.25rem 0.5rem;
+}
+
+.doc-content {
+    color: #555;
+    line-height: 1.8;
+    font-family: 'Segoe UI', Tahoma, Geneva, Verdana, sans-serif;
+}
+
+.description-paragraph {
+    margin-bottom: 1rem;
+    line-height: 1.8;
+}
+
+.description-list {
+    list-style: none;
+    padding-left: 0;
+    margin: 1rem 0;
+}
+
+.description-list li {
+    padding: 0.5rem 0 0.5rem 1.5rem;
+    position: relative;
+    line-height: 1.8;
+    margin-bottom: 0.5rem;
+}
+
+.description-list li::before {
+    content: '•';
+    position: absolute;
+    left: 0;
+    color: #3498db;
+    font-size: 1.2em;
+    font-weight: bold;
+    line-height: 1.4;
+}
+
+.description-list li:last-child {
+    margin-bottom: 0;
+}
+
+/* Ensure Unicode mathematical symbols render correctly */
+.doc-content,
+.math-formula {
+    font-variant-numeric: normal;
+    text-rendering: optimizeLegibility;
+    -webkit-font-feature-settings: "kern" 1;
+    font-feature-settings: "kern" 1;
+}
+
+.syntax-box,
+.example-box {
+    background: #2c3e50;
+    color: #ecf0f1;
+    padding: 1rem;
+    border-radius: 6px;
+    overflow-x: auto;
+    font-family: 'Courier New', monospace;
+    font-size: 0.9rem;
+    line-height: 1.6;
+    margin: 0;
+    white-space: pre-wrap;
+    word-wrap: break-word;
+}
+
+.example-box {
+    background: #34495e;
+    border-left: 4px solid #3498db;
+}
+
+/* Editor Section */
+.cv-editor-section {
+    margin-top: 2rem;
+    border-top: 2px solid #e1e8ed;
+    padding-top: 1.5rem;
+}
+
+.editor-header {
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    margin-bottom: 1rem;
+}
+
+.editor-header h4 {
+    color: #2c3e50;
+    margin: 0;
+    font-size: 1.1rem;
+}
+
+.editor-header h4 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+.editor-actions {
+    display: flex;
+    gap: 0.5rem;
+}
+
+.cv-editor {
+    width: 100%;
+    min-height: 300px;
+    padding: 1rem;
+    border: 2px solid #dee2e6;
+    border-radius: 6px;
+    font-family: 'Courier New', monospace;
+    font-size: 0.9rem;
+    line-height: 1.6;
+    resize: vertical;
+    transition: border-color 0.3s ease;
+}
+
+.cv-editor:focus {
+    outline: none;
+    border-color: #3498db;
+    box-shadow: 0 0 0 3px rgba(52, 152, 219, 0.1);
+}
+
+.editor-footer {
+    display: flex;
+    justify-content: space-between;
+    margin-top: 0.5rem;
+    font-size: 0.85rem;
+    color: #7f8c8d;
+}
+
+/* Saved Configurations */
+.saved-configs {
+    margin-top: 2rem;
+    padding-top: 1.5rem;
+    border-top: 2px solid #e1e8ed;
+}
+
+.saved-configs h4 {
+    color: #2c3e50;
+    margin-bottom: 1rem;
+    font-size: 1.1rem;
+}
+
+.saved-configs h4 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+.config-item {
+    background: #f8f9fa;
+    border: 1px solid #dee2e6;
+    border-radius: 6px;
+    padding: 1rem;
+    margin-bottom: 0.75rem;
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    transition: all 0.3s ease;
+}
+
+.config-item:hover {
+    background: #e3f2fd;
+    border-color: #3498db;
+}
+
+.config-item-name {
+    font-weight: 600;
+    color: #2c3e50;
+}
+
+.config-item-actions {
+    display: flex;
+    gap: 0.5rem;
+}
+
+.config-item-actions button {
+    padding: 0.25rem 0.75rem;
+    font-size: 0.85rem;
+}
+
+/* Section Description */
+.section-description {
+    color: #7f8c8d;
+    margin-bottom: 1.5rem;
+    font-style: italic;
+}
+
+/* Glossary and Options Lists */
+.glossary-content,
+.options-list,
+.components-list {
+    display: flex;
+    flex-direction: column;
+    gap: 1rem;
+}
+
+.glossary-item {
+    background: white;
+    padding: 1rem;
+    border-radius: 6px;
+    border-left: 3px solid #9b59b6;
+    margin-bottom: 0.5rem;
+}
+
+.glossary-item strong {
+    color: #2c3e50;
+    font-size: 1rem;
+    display: inline-block;
+    margin-right: 0.5rem;
+}
+
+.glossary-item p {
+    margin: 0.5rem 0 0 0;
+    color: #555;
+    line-height: 1.6;
+}
+
+.glossary-content > p {
+    font-weight: 600;
+    color: #2c3e50;
+    margin-bottom: 1rem;
+}
+
+/* Options Keywords - Horizontal Layout */
+.options-keywords {
+    display: flex;
+    flex-wrap: wrap;
+    gap: 0.75rem;
+    align-items: center;
+    padding: 1rem;
+    background: #f8f9fa;
+    border-radius: 6px;
+    border: 1px solid #dee2e6;
+}
+
+.options-keywords code {
+    padding: 0.5rem 0.75rem;
+    border-radius: 4px;
+    font-family: 'Courier New', monospace;
+    font-size: 0.9rem;
+    font-weight: 600;
+    white-space: nowrap;
+    display: inline-block;
+    transition: all 0.2s ease;
+}
+
+.keyword-required {
+    background: #fee;
+    color: #c33;
+    border: 1px solid #fcc;
+}
+
+.keyword-required:hover {
+    background: #fdd;
+    border-color: #c33;
+    transform: translateY(-1px);
+    box-shadow: 0 2px 4px rgba(204, 51, 51, 0.2);
+}
+
+.keyword-optional {
+    background: #f5f5f5;
+    color: #666;
+    border: 1px solid #ddd;
+}
+
+.keyword-optional:hover {
+    background: #eee;
+    border-color: #999;
+    transform: translateY(-1px);
+    box-shadow: 0 2px 4px rgba(0, 0, 0, 0.1);
+}
+
+/* Components Lists */
+.components-list {
+    display: flex;
+    flex-direction: column;
+    gap: 1rem;
+}
+
+.component-item {
+    background: white;
+    padding: 1rem;
+    border-radius: 6px;
+    border-left: 3px solid #3498db;
+    margin-bottom: 0.5rem;
+}
+
+.component-item strong {
+    color: #2c3e50;
+    font-size: 1rem;
+    display: inline-block;
+    margin-right: 0.5rem;
+}
+
+.component-item p {
+    margin: 0.5rem 0 0 0;
+    color: #555;
+    line-height: 1.6;
+}
+
+/* Notes List */
+.notes-list {
+    list-style: none;
+    padding: 0;
+}
+
+.notes-list li {
+    padding: 0.75rem;
+    margin-bottom: 0.5rem;
+    background: #fff3cd;
+    border-left: 3px solid #ffc107;
+    border-radius: 4px;
+    color: #856404;
+}
+
+.notes-list li::before {
+    content: "ℹ️";
+    margin-right: 0.5rem;
+}
+
+/* Math Formulas */
+.math-formula {
+    background: #f8f9fa;
+    padding: 0.75rem;
+    border-radius: 4px;
+    margin: 0.75rem 0;
+    font-family: 'Times New Roman', 'DejaVu Serif', serif;
+    font-size: 1rem;
+    border-left: 3px solid #3498db;
+    white-space: pre-wrap;
+    line-height: 1.8;
+    color: #2c3e50;
+    font-style: italic;
+}
+
+/* Mathematical formatting */
+.math-fraction {
+    display: inline-flex;
+    flex-direction: column;
+    vertical-align: middle;
+    text-align: center;
+    margin: 0 0.3em;
+    line-height: 1;
+    font-size: 1.1em;
+}
+
+.math-numerator {
+    border-bottom: 1.5px solid currentColor;
+    padding: 0 0.3em 0.1em 0.3em;
+    line-height: 1.1;
+}
+
+.math-denominator {
+    padding: 0.1em 0.3em 0 0.3em;
+    line-height: 1.1;
+}
+
+.math-sqrt {
+    display: inline-block;
+    position: relative;
+    vertical-align: middle;
+    margin: 0 0.2em;
+    font-size: 1.1em;
+}
+
+.math-sqrt-symbol {
+    font-size: 1.3em;
+    vertical-align: middle;
+    margin-right: 0.1em;
+    line-height: 1;
+}
+
+.math-radicand {
+    display: inline-block;
+    padding: 0.1em 0.3em;
+    margin-left: 0.1em;
+    border-top: 1.5px solid currentColor;
+    vertical-align: middle;
+}
+
+.math-formula sup,
+.math-formula sub,
+.description-paragraph sup,
+.description-paragraph sub,
+.description-list li sup,
+.description-list li sub {
+    font-size: 0.75em;
+    line-height: 0;
+    position: relative;
+    vertical-align: baseline;
+    font-weight: normal;
+}
+
+.math-formula sup,
+.description-paragraph sup,
+.description-list li sup {
+    top: -0.5em;
+}
+
+.math-formula sub,
+.description-paragraph sub,
+.description-list li sub {
+    bottom: -0.25em;
+}
+
+/* Ensure proper rendering of subscripts and superscripts in all contexts */
+.doc-content sup,
+.doc-content sub {
+    font-size: 0.75em;
+    line-height: 0;
+    position: relative;
+    vertical-align: baseline;
+}
+
+.doc-content sup {
+    top: -0.5em;
+}
+
+.doc-content sub {
+    bottom: -0.25em;
+}
+
+.doc-content sub {
+    font-size: 0.8em;
+    vertical-align: sub;
+}
+
+.doc-content code {
+    background: #f1f3f5;
+    padding: 0.2rem 0.4rem;
+    border-radius: 3px;
+    font-family: 'Courier New', monospace;
+    font-size: 0.9em;
+}
+
+/* Related CVs */
+.related-cvs {
+    display: flex;
+    flex-wrap: wrap;
+    gap: 0.5rem;
+}
+
+.related-cv-badge {
+    display: inline-block;
+    padding: 0.5rem 1rem;
+    background: #e3f2fd;
+    color: #1976d2;
+    border-radius: 20px;
+    cursor: pointer;
+    transition: all 0.3s ease;
+    font-weight: 500;
+    border: 1px solid #90caf9;
+}
+
+.related-cv-badge:hover {
+    background: #1976d2;
+    color: white;
+    transform: translateY(-2px);
+    box-shadow: 0 2px 8px rgba(25, 118, 210, 0.3);
+}
+
+/* Responsive Design */
+@media (max-width: 1024px) {
+    .plumed-container {
+        flex-direction: column;
+    }
+    
+    .plumed-sidebar {
+        width: 100%;
+        max-height: 300px;
+    }
+}
+
+/* Scrollbar Styling */
+.cv-list::-webkit-scrollbar,
+.plumed-content::-webkit-scrollbar {
+    width: 8px;
+}
+
+.cv-list::-webkit-scrollbar-track,
+.plumed-content::-webkit-scrollbar-track {
+    background: #f1f1f1;
+    border-radius: 4px;
+}
+
+.cv-list::-webkit-scrollbar-thumb,
+.plumed-content::-webkit-scrollbar-thumb {
+    background: #bdc3c7;
+    border-radius: 4px;
+}
+
+.cv-list::-webkit-scrollbar-thumb:hover,
+.plumed-content::-webkit-scrollbar-thumb:hover {
+    background: #95a5a6;
+}
+
+/* PLUMED Section Cards */
+.plumed-section-card {
+    margin-bottom: 1.5rem;
+}
+
+.plumed-section-card:last-child {
+    margin-bottom: 0;
+}
+
+/* PLUMED Section Headers - Smaller font size */
+.plumed-section-card h2 {
+    font-size: 1.4rem !important;
+}
+
+/* Collapsed state - hide content but keep header visible */
+.plumed-section-card.collapsed .section-description,
+.plumed-section-card.collapsed .plumed-container,
+.plumed-section-card.collapsed .plumed-generate-section,
+.plumed-section-card.collapsed .generate-simulation-files-section {
+    max-height: 0;
+    opacity: 0;
+    margin-top: 0;
+    margin-bottom: 0;
+    padding-top: 0;
+    padding-bottom: 0;
+    overflow: hidden;
+    transition: max-height 0.4s ease, opacity 0.3s ease, margin 0.3s ease, padding 0.3s ease;
+}
+
+/* Keep header visible even when collapsed */
+.plumed-section-card.collapsed .plumed-toggle-header {
+    margin-bottom: 0;
+}
+
+/* Collapsible Header */
+.plumed-toggle-header {
+    cursor: pointer;
+    user-select: none;
+    display: flex;
+    align-items: center;
+    justify-content: space-between;
+    transition: color 0.3s ease;
+    padding: 0.5rem;
+    margin: -0.5rem;
+    border-radius: 4px;
+    text-align: left !important;
+}
+
+.plumed-toggle-header > i:first-of-type {
+    margin-right: 0.5rem;
+}
+
+/* Ensure left alignment for custom PLUMED header */
+#custom-plumed-card h2,
+#custom-plumed-card .plumed-toggle-header {
+    text-align: left !important;
+    justify-content: flex-start !important;
+}
+
+#custom-plumed-card .plumed-toggle-header {
+    display: flex !important;
+    align-items: center;
+}
+
+#custom-plumed-card .plumed-toggle-header > *:first-child {
+    margin-right: 0.5rem;
+}
+
+#custom-plumed-card .plumed-toggle-header .toggle-icon {
+    margin-left: auto;
+    margin-right: 0;
+}
+
+/* Generate Simulation Files Section - Left Aligned */
+#generate-simulation-files-card h2,
+#generate-simulation-files-card .plumed-toggle-header {
+    text-align: left !important;
+    justify-content: flex-start !important;
+}
+
+#generate-simulation-files-card .plumed-toggle-header {
+    display: flex !important;
+    align-items: center;
+}
+
+#generate-simulation-files-card .plumed-toggle-header > *:first-child {
+    margin-right: 0.5rem;
+}
+
+#generate-simulation-files-card .plumed-toggle-header .toggle-icon {
+    margin-left: auto;
+    margin-right: 0;
+}
+
+.plumed-toggle-header:hover {
+    background: rgba(52, 152, 219, 0.1);
+    color: #3498db;
+}
+
+.toggle-icon {
+    transition: transform 0.3s ease;
+    font-size: 0.9em;
+    color: #7f8c8d;
+}
+
+.plumed-toggle-header.collapsed .toggle-icon {
+    transform: rotate(-90deg);
+}
+
+.plumed-container,
+.plumed-generate-section {
+    transition: max-height 0.4s ease, opacity 0.3s ease, margin 0.3s ease;
+    overflow: hidden;
+}
+
+.section-description {
+    transition: max-height 0.4s ease, opacity 0.3s ease, margin 0.3s ease, padding 0.3s ease;
+    overflow: hidden;
+}
+
+/* Generate Files Section */
+.plumed-generate-section {
+    margin-top: 1.5rem;
+    padding-top: 1.5rem;
+}
+
+.generate-content {
+    display: flex;
+    flex-direction: column;
+    gap: 1.5rem;
+}
+
+.generate-options {
+    display: flex;
+    gap: 1rem;
+    flex-wrap: wrap;
+}
+
+.generate-options .btn {
+    padding: 0.75rem 1.5rem;
+    font-size: 1rem;
+    display: flex;
+    align-items: center;
+    gap: 0.5rem;
+}
+
+.generated-file-preview {
+    background: #f8f9fa;
+    border: 1px solid #dee2e6;
+    border-radius: 8px;
+    padding: 1.5rem;
+    margin-top: 1rem;
+}
+
+.generated-file-preview h4 {
+    margin: 0 0 1rem 0;
+    color: #2c3e50;
+    font-size: 1.1rem;
+}
+
+.file-preview {
+    background: #2c3e50;
+    color: #ecf0f1;
+    padding: 1rem;
+    border-radius: 4px;
+    overflow-x: auto;
+    font-family: 'Courier New', monospace;
+    font-size: 0.9rem;
+    line-height: 1.6;
+    margin: 0;
+    max-height: 400px;
+    overflow-y: auto;
+}
+
+/* Custom PLUMED File Section */
+.custom-plumed-section {
+    margin-top: 1.5rem;
+    transition: max-height 0.4s ease, opacity 0.3s ease, margin 0.3s ease, padding 0.3s ease;
+    overflow: hidden;
+}
+
+/* Collapsed state for custom PLUMED section */
+#custom-plumed-card.collapsed .section-description,
+#custom-plumed-card.collapsed .custom-plumed-section {
+    max-height: 0;
+    opacity: 0;
+    margin-top: 0;
+    margin-bottom: 0;
+    padding-top: 0;
+    padding-bottom: 0;
+    overflow: hidden;
+}
+
+/* Keep header visible even when collapsed */
+#custom-plumed-card.collapsed .plumed-toggle-header {
+    margin-bottom: 0;
+}
+
+.custom-editor-header {
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    margin-bottom: 1rem;
+    padding-bottom: 0.75rem;
+    border-bottom: 2px solid #dee2e6;
+}
+
+.custom-editor-header h4 {
+    margin: 0;
+    color: #2c3e50;
+    font-size: 1.1rem;
+    display: flex;
+    align-items: center;
+    gap: 0.5rem;
+}
+
+.custom-editor-header h4 i {
+    color: #3498db;
+}
+
+.custom-plumed-editor {
+    width: 100%;
+    min-height: 400px;
+    padding: 1rem;
+    border: 2px solid #dee2e6;
+    border-radius: 8px;
+    font-family: 'Courier New', monospace;
+    font-size: 0.95rem;
+    line-height: 1.6;
+    resize: vertical;
+    background: #ffffff;
+    color: #2c3e50;
+    transition: border-color 0.3s ease;
+}
+
+.custom-plumed-editor:focus {
+    outline: none;
+    border-color: #3498db;
+    box-shadow: 0 0 0 3px rgba(52, 152, 219, 0.1);
+}
+
+.custom-plumed-editor::placeholder {
+    color: #95a5a6;
+    font-style: italic;
+}
+

ambermdflow/css/styles.css

@@ -0,0 +1,2029 @@
+/* Reset and Base Styles */
+* {
+    margin: 0;
+    padding: 0;
+    box-sizing: border-box;
+}
+
+body {
+    font-family: 'Segoe UI', Tahoma, Geneva, Verdana, sans-serif;
+    line-height: 1.6;
+    color: #333;
+    background: linear-gradient(135deg, #667eea 0%, #764ba2 100%);
+    min-height: 100vh;
+}
+
+.container {
+    max-width: 1400px;
+    margin: 0 auto;
+    background: white;
+    min-height: 100vh;
+    box-shadow: 0 0 30px rgba(0, 0, 0, 0.1);
+}
+
+/* Header Styles */
+.header {
+    background: linear-gradient(135deg, #2c3e50 0%, #3498db 100%);
+    color: white;
+    padding: 2rem 0;
+    text-align: center;
+    box-shadow: 0 4px 6px rgba(0, 0, 0, 0.1);
+}
+
+.header-content h1 {
+    font-size: 2.5rem;
+    margin-bottom: 0.5rem;
+    font-weight: 300;
+}
+
+.header-content p {
+    font-size: 1.1rem;
+    opacity: 0.9;
+}
+
+.header i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+/* Tab Navigation */
+.tab-navigation {
+    display: flex;
+    background: #34495e;
+    border-bottom: 3px solid #3498db;
+    overflow-x: auto;
+}
+
+/* Step Navigation Controls */
+.step-navigation {
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    background: #ffffff;
+    padding: 20px 30px;
+    border-top: 1px solid #dee2e6;
+    box-shadow: 0 -2px 8px rgba(0,0,0,0.1);
+    position: sticky;
+    bottom: 0;
+    z-index: 100;
+}
+
+/* Checkbox with Button Layout */
+.checkbox-with-button {
+    display: flex;
+    align-items: center;
+    gap: 15px;
+    margin-bottom: 10px;
+}
+
+.checkbox-with-button .checkbox-container {
+    margin-bottom: 0;
+    flex: 1;
+}
+
+.btn-sm {
+    padding: 6px 12px;
+    font-size: 12px;
+    border-radius: 4px;
+}
+
+.btn-outline-primary {
+    color: #007bff;
+    border: 1px solid #007bff;
+    background: transparent;
+}
+
+.btn-outline-primary:hover:not(:disabled) {
+    color: white;
+    background: #007bff;
+    border-color: #007bff;
+}
+
+.btn-outline-primary:disabled {
+    color: #6c757d;
+    border-color: #6c757d;
+    background: transparent;
+    cursor: not-allowed;
+}
+
+.nav-btn {
+    display: flex;
+    align-items: center;
+    gap: 8px;
+    padding: 10px 20px;
+    border: 2px solid #007bff;
+    background: #007bff;
+    color: white;
+    border-radius: 25px;
+    font-weight: 600;
+    cursor: pointer;
+    transition: all 0.3s ease;
+    font-size: 14px;
+}
+
+.nav-btn:hover:not(:disabled) {
+    background: #0056b3;
+    border-color: #0056b3;
+    transform: translateY(-2px);
+    box-shadow: 0 4px 8px rgba(0,123,255,0.3);
+}
+
+.nav-btn:disabled {
+    background: #6c757d;
+    border-color: #6c757d;
+    cursor: not-allowed;
+    opacity: 0.6;
+}
+
+.step-indicator {
+    display: flex;
+    align-items: center;
+    gap: 5px;
+    font-weight: 600;
+    color: #495057;
+    font-size: 16px;
+}
+
+.step-indicator span {
+    background: #e9ecef;
+    padding: 8px 12px;
+    border-radius: 20px;
+    min-width: 30px;
+    text-align: center;
+}
+
+.step-indicator #current-step {
+    background: #007bff;
+    color: white;
+}
+
+.tab-button {
+    flex: 1;
+    background: none;
+    border: none;
+    color: white;
+    padding: 1rem 1.5rem;
+    cursor: pointer;
+    font-size: 1rem;
+    font-weight: 500;
+    transition: all 0.3s ease;
+    border-bottom: 3px solid transparent;
+    min-width: 200px;
+}
+
+.tab-button:hover {
+    background: rgba(255, 255, 255, 0.1);
+    transform: translateY(-2px);
+}
+
+.tab-button.active {
+    background: #3498db;
+    border-bottom-color: #e74c3c;
+    transform: translateY(-2px);
+}
+
+.tab-button i {
+    margin-right: 0.5rem;
+    font-size: 1.1rem;
+}
+
+/* Main Content */
+.main-content {
+    padding: 2rem;
+    min-height: 600px;
+}
+
+.tab-content {
+    display: none;
+    animation: fadeIn 0.5s ease-in-out;
+}
+
+.tab-content.active {
+    display: block;
+}
+
+@keyframes fadeIn {
+    from { opacity: 0; transform: translateY(20px); }
+    to { opacity: 1; transform: translateY(0); }
+}
+
+/* Card Styles */
+.card {
+    background: white;
+    border-radius: 12px;
+    box-shadow: 0 8px 25px rgba(0, 0, 0, 0.1);
+    padding: 2rem;
+    margin-bottom: 2rem;
+    border: 1px solid #e1e8ed;
+}
+
+.card h2 {
+    color: #2c3e50;
+    margin-bottom: 1.5rem;
+    font-size: 1.8rem;
+    font-weight: 600;
+    border-bottom: 2px solid #3498db;
+    padding-bottom: 0.5rem;
+}
+
+.card h2 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+/* File Generation Note */
+.file-generation-note {
+    background: #fff3cd;
+    border: 2px solid #ffc107;
+    border-left: 5px solid #ffc107;
+    border-radius: 8px;
+    padding: 1rem 1.5rem;
+    margin-bottom: 1.5rem;
+    display: flex;
+    align-items: flex-start;
+    gap: 1rem;
+    box-shadow: 0 2px 4px rgba(255, 193, 7, 0.1);
+}
+
+.file-generation-note i {
+    color: #856404;
+    font-size: 1.5rem;
+    margin-top: 0.2rem;
+    flex-shrink: 0;
+}
+
+.file-generation-note .note-content {
+    flex: 1;
+    color: #856404;
+    line-height: 1.6;
+}
+
+.file-generation-note .note-content p {
+    margin: 0;
+    font-size: 0.95rem;
+}
+
+.file-generation-note .note-content strong {
+    color: #664d03;
+    font-weight: 600;
+}
+
+/* Protein Loading Styles */
+.input-methods {
+    display: grid;
+    grid-template-columns: 1fr auto 1fr;
+    gap: 2rem;
+    align-items: center;
+    margin-bottom: 2rem;
+}
+
+.method-option {
+    background: #f8f9fa;
+    padding: 1.5rem;
+    border-radius: 8px;
+    border: 2px dashed #dee2e6;
+    transition: all 0.3s ease;
+}
+
+.method-option:hover {
+    border-color: #3498db;
+    background: #f0f8ff;
+}
+
+.method-option h3 {
+    color: #2c3e50;
+    margin-bottom: 1rem;
+    font-size: 1.2rem;
+}
+
+.method-option h3 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+.divider {
+    text-align: center;
+    font-weight: bold;
+    color: #7f8c8d;
+    font-size: 1.1rem;
+}
+
+.divider::before,
+.divider::after {
+    content: '';
+    display: inline-block;
+    width: 50px;
+    height: 2px;
+    background: #bdc3c7;
+    vertical-align: middle;
+    margin: 0 1rem;
+}
+
+/* File Upload Area */
+.file-upload-area {
+    border: 2px dashed #3498db;
+    border-radius: 8px;
+    padding: 2rem;
+    text-align: center;
+    cursor: pointer;
+    transition: all 0.3s ease;
+    background: #f8f9fa;
+}
+
+.file-upload-area:hover {
+    background: #e3f2fd;
+    border-color: #2980b9;
+}
+
+.file-upload-area i {
+    font-size: 3rem;
+    color: #3498db;
+    margin-bottom: 1rem;
+    display: block;
+}
+
+.file-upload-area p {
+    margin-bottom: 1rem;
+    color: #7f8c8d;
+}
+
+.file-info {
+    background: #d4edda;
+    border: 1px solid #c3e6cb;
+    border-radius: 4px;
+    padding: 1rem;
+    margin-top: 1rem;
+}
+
+.file-info p {
+    margin: 0.25rem 0;
+    color: #155724;
+}
+
+/* PDB Fetch */
+.pdb-fetch {
+    margin-top: 1rem;
+}
+
+.input-group {
+    display: flex;
+    gap: 1rem;
+    align-items: end;
+}
+
+.input-group label {
+    font-weight: 600;
+    color: #2c3e50;
+    margin-bottom: 0.5rem;
+    display: block;
+}
+
+.input-group input {
+    flex: 1;
+    padding: 0.75rem;
+    border: 2px solid #dee2e6;
+    border-radius: 4px;
+    font-size: 1rem;
+    transition: border-color 0.3s ease;
+}
+
+.input-group input:focus {
+    outline: none;
+    border-color: #3498db;
+    box-shadow: 0 0 0 3px rgba(52, 152, 219, 0.1);
+}
+
+/* Status Messages */
+.status-message {
+    margin-top: 1rem;
+    padding: 0.75rem;
+    border-radius: 4px;
+    font-weight: 500;
+}
+
+.status-message.success {
+    background: #d4edda;
+    color: #155724;
+    border: 1px solid #c3e6cb;
+}
+
+.status-message.error {
+    background: #f8d7da;
+    color: #721c24;
+    border: 1px solid #f5c6cb;
+}
+
+.status-message.info {
+    background: #d1ecf1;
+    color: #0c5460;
+    border: 1px solid #bee5eb;
+}
+
+/* Protein Preview */
+.protein-preview {
+    margin-top: 2rem;
+    background: #f8f9fa;
+    border-radius: 8px;
+    padding: 1.5rem;
+    border: 1px solid #dee2e6;
+}
+
+.preview-content {
+    display: grid;
+    grid-template-columns: 1fr 1fr;
+    gap: 2rem;
+    margin-top: 1rem;
+}
+
+/* Structure comparison container - force side by side and centered */
+.structure-comparison-container {
+    display: flex !important;
+    flex-direction: row !important;
+    width: 100% !important;
+    max-width: 1400px !important;
+    gap: 20px !important;
+    margin: 0 auto !important;
+    justify-content: center !important;
+}
+
+.structure-comparison-container .comparison-viewer {
+    flex: 0 1 48% !important;
+    min-width: 450px !important;
+    max-width: 48% !important;
+}
+
+/* Override preview-content for comparison view */
+#completed-structure-preview .preview-content {
+    display: flex !important;
+    justify-content: center !important;
+    width: 100% !important;
+    padding: 0 !important;
+    grid-template-columns: none !important;
+}
+
+.protein-info p {
+    margin: 0.5rem 0;
+    font-size: 1rem;
+}
+
+.protein-visualization {
+    background: white;
+    border-radius: 4px;
+    padding: 1rem;
+    border: 1px solid #dee2e6;
+    min-height: 300px;
+    position: relative;
+}
+
+/* Ensure NGL viewer controls overlay within both original and prepared viewers */
+.molecule-viewer {
+    position: relative;
+}
+
+#ngl-viewer {
+    border-radius: 4px;
+    background: #f8f9fa;
+    border: 1px solid #dee2e6;
+}
+
+.viewer-controls {
+    position: absolute;
+    top: 10px;
+    right: 10px;
+    display: flex;
+    gap: 0.5rem;
+    z-index: 10;
+}
+
+.viewer-controls .btn {
+    padding: 0.25rem 0.5rem;
+    font-size: 0.8rem;
+    border-radius: 3px;
+    box-shadow: 0 2px 4px rgba(0,0,0,0.1);
+}
+
+.viewer-controls .btn:hover {
+    transform: translateY(-1px);
+    box-shadow: 0 4px 8px rgba(0,0,0,0.15);
+}
+
+/* Superimposed structure preview: controls inside the viewer box (parent has position: relative) */
+#superimposed-molecule-viewer .viewer-controls {
+    position: absolute;
+    top: 10px;
+    right: 10px;
+    z-index: 10;
+}
+
+/* Simulation Parameters */
+.params-grid {
+    display: grid;
+    grid-template-columns: repeat(auto-fit, minmax(300px, 1fr));
+    gap: 2rem;
+}
+
+.param-section {
+    background: #f8f9fa;
+    padding: 1.5rem;
+    border-radius: 8px;
+    border: 1px solid #dee2e6;
+}
+
+.param-section h3 {
+    color: #2c3e50;
+    margin-bottom: 1rem;
+    font-size: 1.2rem;
+    border-bottom: 1px solid #bdc3c7;
+    padding-bottom: 0.5rem;
+}
+
+.param-section h3 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+.form-group {
+    margin-bottom: 1rem;
+}
+
+.form-group label {
+    display: block;
+    margin-bottom: 0.5rem;
+    font-weight: 600;
+    color: #2c3e50;
+}
+
+.form-group input,
+.form-group select {
+    width: 100%;
+    padding: 0.75rem;
+    border: 2px solid #dee2e6;
+    border-radius: 4px;
+    font-size: 1rem;
+    transition: border-color 0.3s ease;
+}
+
+.form-group input:focus,
+.form-group select:focus {
+    outline: none;
+    border-color: #3498db;
+    box-shadow: 0 0 0 3px rgba(52, 152, 219, 0.1);
+}
+
+/* Simulation Steps */
+.steps-container {
+    display: flex;
+    flex-direction: column;
+    gap: 1.5rem;
+}
+
+.step-item {
+    background: #f8f9fa;
+    border-radius: 8px;
+    border: 1px solid #dee2e6;
+    overflow: hidden;
+    transition: all 0.3s ease;
+}
+
+.step-item:hover {
+    box-shadow: 0 4px 12px rgba(0, 0, 0, 0.1);
+    transform: translateY(-2px);
+}
+
+.step-header {
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    padding: 1.5rem;
+    background: #34495e;
+    color: white;
+    cursor: pointer;
+}
+
+.step-header h3 {
+    margin: 0;
+    font-size: 1.2rem;
+    font-weight: 600;
+}
+
+.step-header h3 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+.step-content {
+    padding: 1.5rem;
+    background: white;
+    display: none;
+}
+
+.step-content.active {
+    display: block;
+}
+
+.form-row {
+    display: grid;
+    grid-template-columns: repeat(auto-fit, minmax(200px, 1fr));
+    gap: 1rem;
+}
+
+/* Toggle Switch */
+.switch {
+    position: relative;
+    display: inline-block;
+    width: 60px;
+    height: 34px;
+}
+
+.switch input {
+    opacity: 0;
+    width: 0;
+    height: 0;
+}
+
+.slider {
+    position: absolute;
+    cursor: pointer;
+    top: 0;
+    left: 0;
+    right: 0;
+    bottom: 0;
+    background-color: #ccc;
+    transition: .4s;
+    border-radius: 34px;
+}
+
+.slider:before {
+    position: absolute;
+    content: "";
+    height: 26px;
+    width: 26px;
+    left: 4px;
+    bottom: 4px;
+    background-color: white;
+    transition: .4s;
+    border-radius: 50%;
+}
+
+input:checked + .slider {
+    background-color: #3498db;
+}
+
+input:checked + .slider:before {
+    transform: translateX(26px);
+}
+
+/* File Generation */
+.generation-controls {
+    display: flex;
+    gap: 1rem;
+    margin-bottom: 2rem;
+    flex-wrap: wrap;
+}
+
+.files-preview {
+    margin-bottom: 2rem;
+}
+
+.files-list {
+    display: grid;
+    grid-template-columns: repeat(auto-fill, minmax(300px, 1fr));
+    gap: 1rem;
+    margin-top: 1rem;
+}
+
+.file-item {
+    background: #f8f9fa;
+    border: 1px solid #dee2e6;
+    border-radius: 8px;
+    padding: 1rem;
+    transition: all 0.3s ease;
+}
+
+.file-item:hover {
+    background: #e3f2fd;
+    border-color: #3498db;
+    transform: translateY(-2px);
+}
+
+.file-item h4 {
+    color: #2c3e50;
+    margin-bottom: 0.5rem;
+    font-size: 1.1rem;
+}
+
+.file-item p {
+    color: #7f8c8d;
+    font-size: 0.9rem;
+    margin: 0.25rem 0;
+}
+
+.download-section {
+    margin-bottom: 2rem;
+}
+
+.download-options {
+    display: flex;
+    gap: 1rem;
+    flex-wrap: wrap;
+    margin-top: 1rem;
+}
+
+.simulation-summary {
+    background: #f8f9fa;
+    border-radius: 8px;
+    padding: 1.5rem;
+    border: 1px solid #dee2e6;
+}
+
+.summary-content {
+    display: grid;
+    grid-template-columns: repeat(auto-fit, minmax(250px, 1fr));
+    gap: 1rem;
+    margin-top: 1rem;
+}
+
+.summary-item {
+    background: white;
+    padding: 1rem;
+    border-radius: 4px;
+    border: 1px solid #dee2e6;
+}
+
+.summary-item h4 {
+    color: #2c3e50;
+    margin-bottom: 0.5rem;
+    font-size: 1rem;
+}
+
+.summary-item p {
+    color: #7f8c8d;
+    margin: 0.25rem 0;
+}
+
+/* Checkbox Group Styles */
+.checkbox-group {
+    display: flex;
+    gap: 1rem;
+    margin-top: 0.5rem;
+}
+
+.checkbox-container {
+    display: flex;
+    align-items: center;
+    cursor: pointer;
+    font-size: 0.9rem;
+    color: #495057;
+}
+
+.checkbox-container input[type="checkbox"] {
+    margin-right: 0.5rem;
+    transform: scale(1.2);
+}
+
+.checkbox-container:hover {
+    color: #007bff;
+}
+
+/* Ion Controls */
+.ion-controls {
+    display: flex;
+    gap: 0.5rem;
+    align-items: center;
+}
+
+.ion-controls select {
+    flex: 1;
+}
+
+
+
+
+#ligand-forcefield-section {
+    transition: all 0.3s ease;
+}
+
+#ligand-forcefield-section.disabled {
+    opacity: 0.5;
+    pointer-events: none;
+}
+
+/* Tooltip styling for better text wrapping */
+.tooltip {
+    max-width: 300px;
+}
+
+.tooltip-inner {
+    text-align: left;
+    white-space: normal;
+    word-wrap: break-word;
+}
+
+/* Button Styles */
+.btn {
+    display: inline-flex;
+    align-items: center;
+    padding: 0.75rem 1.5rem;
+    border: none;
+    border-radius: 6px;
+    font-size: 1rem;
+    font-weight: 600;
+    cursor: pointer;
+    transition: all 0.3s ease;
+    text-decoration: none;
+    gap: 0.5rem;
+}
+
+.btn:hover {
+    transform: translateY(-2px);
+    box-shadow: 0 4px 12px rgba(0, 0, 0, 0.15);
+}
+
+.btn:active {
+    transform: translateY(0);
+}
+
+.btn-primary {
+    background: linear-gradient(135deg, #3498db, #2980b9);
+    color: white;
+}
+
+.btn-primary:hover {
+    background: linear-gradient(135deg, #2980b9, #1f618d);
+}
+
+.btn-secondary {
+    background: linear-gradient(135deg, #95a5a6, #7f8c8d);
+    color: white;
+}
+
+.btn-secondary:hover {
+    background: linear-gradient(135deg, #7f8c8d, #6c7b7d);
+}
+
+.btn-success {
+    background: linear-gradient(135deg, #27ae60, #229954);
+    color: white;
+}
+
+.btn-success:hover {
+    background: linear-gradient(135deg, #229954, #1e8449);
+}
+
+.btn-info {
+    background: linear-gradient(135deg, #17a2b8, #138496);
+    color: white;
+}
+
+.btn-info:hover {
+    background: linear-gradient(135deg, #138496, #117a8b);
+}
+
+.btn i {
+    font-size: 1rem;
+}
+
+/* Footer */
+.footer {
+    background: #2c3e50;
+    color: white;
+    text-align: center;
+    padding: 2rem;
+    margin-top: 2rem;
+}
+
+.footer p {
+    margin: 0;
+    opacity: 0.8;
+}
+
+/* Responsive Design */
+@media (max-width: 768px) {
+    .container {
+        margin: 0;
+        box-shadow: none;
+    }
+    
+    .header-content h1 {
+        font-size: 2rem;
+    }
+    
+    .tab-navigation {
+        flex-direction: column;
+    }
+    
+    .tab-button {
+        min-width: auto;
+        border-bottom: 1px solid #2c3e50;
+    }
+    
+    .main-content {
+        padding: 1rem;
+    }
+    
+    .input-methods {
+        grid-template-columns: 1fr;
+    }
+    
+    .divider {
+        order: 2;
+    }
+    
+    .preview-content {
+        grid-template-columns: 1fr;
+    }
+    
+    .params-grid {
+        grid-template-columns: 1fr;
+    }
+    
+    .form-row {
+        grid-template-columns: 1fr;
+    }
+    
+    .generation-controls {
+        flex-direction: column;
+    }
+    
+    .download-options {
+        flex-direction: column;
+    }
+    
+    .summary-content {
+        grid-template-columns: 1fr;
+    }
+}
+
+@media (max-width: 480px) {
+    .header-content h1 {
+        font-size: 1.5rem;
+    }
+    
+    .card {
+        padding: 1rem;
+    }
+    
+    .card h2 {
+        font-size: 1.5rem;
+    }
+    
+    .btn {
+        padding: 0.5rem 1rem;
+        font-size: 0.9rem;
+    }
+}
+
+/* Loading Animation */
+.loading {
+    display: inline-block;
+    width: 20px;
+    height: 20px;
+    border: 3px solid #f3f3f3;
+    border-top: 3px solid #3498db;
+    border-radius: 50%;
+    animation: spin 1s linear infinite;
+}
+
+@keyframes spin {
+    0% { transform: rotate(0deg); }
+    100% { transform: rotate(360deg); }
+}
+
+/* Structure Preparation Styles */
+.card-description {
+    color: #7f8c8d;
+    margin-bottom: 2rem;
+    font-style: italic;
+}
+
+.prep-sections {
+    display: grid;
+    grid-template-columns: repeat(auto-fit, minmax(300px, 1fr));
+    gap: 2rem;
+    margin-bottom: 2rem;
+}
+
+.prep-section {
+    background: #f8f9fa;
+    border-radius: 8px;
+    padding: 1.5rem;
+    border: 1px solid #dee2e6;
+}
+
+.prep-section h3 {
+    color: #2c3e50;
+    margin-bottom: 1rem;
+    font-size: 1.2rem;
+    border-bottom: 1px solid #bdc3c7;
+    padding-bottom: 0.5rem;
+}
+
+.prep-section h3 i {
+    margin-right: 0.5rem;
+    color: #3498db;
+}
+
+.prep-section-fullwidth {
+    width: 100%;
+    margin-top: 1rem;
+    margin-bottom: 2rem;
+}
+
+.prep-options {
+    display: flex;
+    flex-direction: column;
+    gap: 1rem;
+}
+
+.prep-option {
+    background: white;
+    border-radius: 6px;
+    padding: 1rem;
+    border: 1px solid #e1e8ed;
+    transition: all 0.3s ease;
+}
+
+.prep-option:hover {
+    box-shadow: 0 2px 8px rgba(0, 0, 0, 0.1);
+    transform: translateY(-1px);
+}
+
+.checkbox-container {
+    display: flex;
+    align-items: center;
+    cursor: pointer;
+    font-weight: 600;
+    color: #2c3e50;
+    margin-bottom: 0.5rem;
+}
+
+.checkbox-container input[type="checkbox"] {
+    margin-right: 0.75rem;
+    transform: scale(1.2);
+}
+
+.option-description {
+    color: #7f8c8d;
+    font-size: 0.9rem;
+    margin: 0;
+    margin-left: 1.5rem;
+}
+
+.prep-actions {
+    display: flex;
+    gap: 1rem;
+    margin-bottom: 2rem;
+    flex-wrap: wrap;
+}
+
+.prep-status {
+    background: #e8f5e8;
+    border: 1px solid #c3e6cb;
+    border-radius: 8px;
+    padding: 1.5rem;
+    margin-bottom: 2rem;
+}
+
+.prep-status h3 {
+    color: #155724;
+    margin-bottom: 1rem;
+}
+
+.status-content {
+    color: #155724;
+}
+
+.prepared-structure-preview {
+    background: #f8f9fa;
+    border-radius: 8px;
+    padding: 1.5rem;
+    border: 1px solid #dee2e6;
+    margin-top: 2rem;
+    width: 100%;
+    box-sizing: border-box;
+}
+
+#sequence-viewer-section {
+    width: 100%;
+    box-sizing: border-box;
+}
+
+.prepared-structure-preview h3 {
+    color: #2c3e50;
+    margin-bottom: 1rem;
+    font-size: 1.2rem;
+}
+
+.structure-info p {
+    margin: 0.5rem 0;
+    font-size: 1rem;
+}
+
+.structure-visualization {
+    margin-top: 1rem;
+}
+
+#prepared-ngl-viewer {
+    border-radius: 4px;
+    background: #f8f9fa;
+    border: 1px solid #dee2e6;
+}
+
+/* Custom Checkbox Styles */
+.checkbox-container input[type="checkbox"] {
+    appearance: none;
+    width: 20px;
+    height: 20px;
+    border: 2px solid #bdc3c7;
+    border-radius: 4px;
+    background: white;
+    position: relative;
+    cursor: pointer;
+    transition: all 0.3s ease;
+}
+
+.checkbox-container input[type="checkbox"]:checked {
+    background: #3498db;
+    border-color: #3498db;
+}
+
+.checkbox-container input[type="checkbox"]:checked::after {
+    content: '✓';
+    position: absolute;
+    top: 50%;
+    left: 50%;
+    transform: translate(-50%, -50%);
+    color: white;
+    font-weight: bold;
+    font-size: 14px;
+}
+
+.checkbox-container input[type="checkbox"]:hover {
+    border-color: #3498db;
+    box-shadow: 0 0 0 3px rgba(52, 152, 219, 0.1);
+}
+
+/* Responsive Design for Structure Prep */
+@media (max-width: 768px) {
+    .prep-sections {
+        grid-template-columns: 1fr;
+    }
+    
+    .prep-actions {
+        flex-direction: column;
+    }
+    
+    .prep-option {
+        padding: 0.75rem;
+    }
+    
+    .option-description {
+        margin-left: 1.25rem;
+    }
+}
+
+/* Utility Classes */
+.text-center { text-align: center; }
+.text-left { text-align: left; }
+.text-right { text-align: right; }
+.mt-1 { margin-top: 0.5rem; }
+.mt-2 { margin-top: 1rem; }
+.mt-3 { margin-top: 1.5rem; }
+.mb-1 { margin-bottom: 0.5rem; }
+.mb-2 { margin-bottom: 1rem; }
+.mb-3 { margin-bottom: 1.5rem; }
+.p-1 { padding: 0.5rem; }
+.p-2 { padding: 1rem; }
+.p-3 { padding: 1.5rem; }
+
+/* Missing Residues Horizontal Display */
+.missing-residues-horizontal {
+    display: inline;
+    color: #155724;
+    font-weight: bold;
+    font-size: 0.95rem;
+    word-wrap: break-word;
+    white-space: normal;
+    line-height: 1.6;
+    margin: 0;
+    padding: 0;
+}
+
+.chain-missing-info {
+    margin-bottom: 1.5rem;
+}
+
+.chain-missing-info h4 {
+    color: #155724;
+    margin-bottom: 0.5rem;
+}
+
+/* Sequence Viewer Styles */
+.sequence-viewer-container {
+    background: #ffffff;
+    border: 1px solid #dee2e6;
+    border-radius: 8px;
+    padding: 1.5rem;
+    max-height: 600px;
+    overflow-y: auto;
+    font-family: 'Courier New', monospace;
+    width: 100%;
+    box-sizing: border-box;
+}
+
+.sequence-chain-container {
+    margin-bottom: 2rem;
+    border-bottom: 2px solid #e9ecef;
+    padding-bottom: 1.5rem;
+}
+
+.sequence-chain-container:last-child {
+    border-bottom: none;
+    margin-bottom: 0;
+}
+
+.sequence-chain-header {
+    margin-bottom: 1rem;
+}
+
+.sequence-chain-header h4 {
+    margin: 0;
+    font-size: 1.1rem;
+    font-weight: 600;
+}
+
+.sequence-display {
+    background: #f8f9fa;
+    border: 1px solid #dee2e6;
+    border-radius: 4px;
+    padding: 1rem;
+    font-size: 14px;
+    line-height: 1.8;
+    width: 100%;
+    box-sizing: border-box;
+}
+
+.sequence-line {
+    display: flex;
+    margin-bottom: 2px;
+    white-space: nowrap;
+}
+
+.sequence-line-number {
+    color: #6c757d;
+    margin-right: 1rem;
+    min-width: 60px;
+    text-align: right;
+    font-size: 12px;
+    user-select: none;
+}
+
+.sequence-characters {
+    letter-spacing: 2px;
+    word-spacing: 0;
+    flex: 1;
+    overflow-x: auto;
+    min-width: 0;
+}
+
+.sequence-char {
+    display: inline-block;
+    padding: 2px 1px;
+    transition: background-color 0.2s;
+}
+
+.sequence-char:hover {
+    background-color: rgba(0, 0, 0, 0.1);
+    border-radius: 2px;
+}
+
+/* Trim Residues Section */
+.trim-info-box {
+    background: #e7f3ff;
+    border: 1px solid #b3d9ff;
+    border-radius: 6px;
+    padding: 1rem;
+    margin-top: 1rem;
+    margin-bottom: 1rem;
+    color: #004085;
+    font-size: 0.9rem;
+    line-height: 1.6;
+}
+
+.trim-info-box i {
+    color: #0066cc;
+    margin-right: 0.5rem;
+}
+
+.trim-info-box strong {
+    color: #003366;
+}
+
+.trim-residues-container {
+    margin-top: 1rem;
+    display: grid;
+    grid-template-columns: repeat(auto-fit, minmax(300px, 1fr));
+    gap: 1rem;
+}
+
+.trim-chain-controls {
+    background: #f8f9fa;
+    border: 1px solid #dee2e6;
+    border-radius: 6px;
+    padding: 1rem;
+}
+
+.trim-chain-controls h5 {
+    color: #2c3e50;
+    margin-bottom: 0.75rem;
+    font-size: 1rem;
+}
+
+.trim-inputs {
+    display: flex;
+    gap: 1.5rem;
+    align-items: center;
+    flex-wrap: wrap;
+}
+
+.trim-input-group {
+    display: flex;
+    align-items: center;
+    gap: 0.5rem;
+}
+
+.trim-input-group label {
+    font-weight: 600;
+    color: #495057;
+    font-size: 0.9rem;
+    min-width: 100px;
+}
+
+.trim-limit {
+    font-weight: normal;
+    color: #6c757d;
+    font-size: 0.85rem;
+    font-style: italic;
+}
+
+.trim-input-group input[type="number"] {
+    width: 80px;
+    padding: 0.5rem;
+    border: 1px solid #ced4da;
+    border-radius: 4px;
+    font-size: 0.9rem;
+}
+
+.trim-input-group input[type="number"]:focus {
+    outline: none;
+    border-color: #3498db;
+    box-shadow: 0 0 0 3px rgba(52, 152, 219, 0.1);
+}
+
+.trim-info {
+    font-size: 0.85rem;
+    color: #6c757d;
+    margin-top: 0.5rem;
+    font-style: italic;
+}
+
+/* Log Modal Styles */
+.log-modal {
+    display: none;
+    position: fixed;
+    z-index: 10000;
+    left: 0;
+    top: 0;
+    width: 100%;
+    height: 100%;
+    background-color: rgba(0, 0, 0, 0.5);
+    animation: fadeIn 0.3s;
+}
+
+@keyframes fadeIn {
+    from { opacity: 0; }
+    to { opacity: 1; }
+}
+
+.log-modal-content {
+    background-color: #fefefe;
+    margin: 2% auto;
+    padding: 0;
+    border: 1px solid #888;
+    border-radius: 8px;
+    width: 90%;
+    max-width: 900px;
+    max-height: 90vh;
+    display: flex;
+    flex-direction: column;
+    box-shadow: 0 4px 20px rgba(0, 0, 0, 0.3);
+    animation: slideDown 0.3s;
+}
+
+@keyframes slideDown {
+    from {
+        transform: translateY(-50px);
+        opacity: 0;
+    }
+    to {
+        transform: translateY(0);
+        opacity: 1;
+    }
+}
+
+.log-modal-header {
+    background: linear-gradient(135deg, #2c3e50 0%, #3498db 100%);
+    color: white;
+    padding: 1rem 1.5rem;
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    border-radius: 8px 8px 0 0;
+}
+
+.log-modal-header h3 {
+    margin: 0;
+    font-size: 1.3rem;
+    font-weight: 500;
+}
+
+.log-modal-close {
+    color: white;
+    font-size: 2rem;
+    font-weight: bold;
+    background: none;
+    border: none;
+    cursor: pointer;
+    padding: 0;
+    width: 30px;
+    height: 30px;
+    display: flex;
+    align-items: center;
+    justify-content: center;
+    border-radius: 50%;
+    transition: background-color 0.2s;
+}
+
+.log-modal-close:hover {
+    background-color: rgba(255, 255, 255, 0.2);
+}
+
+.log-container {
+    flex: 1;
+    overflow-y: auto;
+    padding: 1rem;
+    background-color: #1e1e1e;
+    color: #d4d4d4;
+    font-family: 'Courier New', monospace;
+    font-size: 0.9rem;
+    line-height: 1.6;
+    max-height: calc(90vh - 80px);
+}
+
+.log-content {
+    min-height: 100%;
+}
+
+.log-line {
+    padding: 0.3rem 0;
+    border-bottom: 1px solid rgba(255, 255, 255, 0.05);
+    word-wrap: break-word;
+}
+
+.log-line:last-child {
+    border-bottom: none;
+}
+
+.log-time {
+    color: #858585;
+    margin-right: 0.5rem;
+}
+
+.log-icon {
+    margin-right: 0.5rem;
+}
+
+.log-message {
+    color: #d4d4d4;
+}
+
+.log-info .log-message {
+    color: #d4d4d4;
+}
+
+.log-success .log-message {
+    color: #4ec9b0;
+}
+
+.log-warning .log-message {
+    color: #dcdcaa;
+}
+
+.log-error .log-message {
+    color: #f48771;
+}
+
+.log-result {
+    margin-top: 1.5rem;
+    padding: 1rem;
+    background-color: #252526;
+    border-left: 4px solid #4ec9b0;
+    border-radius: 4px;
+}
+
+.log-result h4 {
+    color: #4ec9b0;
+    margin-bottom: 0.5rem;
+}
+
+.log-result p {
+    color: #d4d4d4;
+    margin: 0.5rem 0;
+}
+
+.log-result ul {
+    margin: 0.5rem 0;
+    padding-left: 1.5rem;
+    color: #d4d4d4;
+}
+
+.log-result li {
+    margin: 0.5rem 0;
+}
+
+/* File Editor Modal Styles */
+#file-content-modal {
+    animation: fadeIn 0.3s;
+}
+
+#file-content-modal > div {
+    animation: slideDown 0.3s;
+}
+
+#modal-content-edit {
+    line-height: 1.6;
+    tab-size: 4;
+    -moz-tab-size: 4;
+}
+
+#modal-content-edit:focus {
+    outline: none;
+    border-color: #0056b3;
+    box-shadow: 0 0 0 3px rgba(0, 123, 255, 0.25);
+}
+
+#save-status {
+    font-weight: 500;
+    animation: slideUp 0.3s;
+}
+
+@keyframes slideUp {
+    from {
+        opacity: 0;
+        transform: translateY(10px);
+    }
+    to {
+        opacity: 1;
+        transform: translateY(0);
+    }
+}
+
+#edit-file-btn:hover {
+    background: #0056b3 !important;
+}
+
+#save-file-btn:hover {
+    background: #218838 !important;
+}
+
+#cancel-edit-btn:hover {
+    background: #5a6268 !important;
+}
+
+/* Frozen/Disabled Checkboxes - Gray only the checkbox, keep text bold and normal */
+.checkbox-container input[type="checkbox"]:disabled {
+    opacity: 0.5 !important;
+    cursor: not-allowed !important;
+    pointer-events: none !important;
+    -webkit-appearance: none !important;
+    appearance: none !important;
+}
+
+.checkbox-container input[type="checkbox"]:disabled + .checkmark {
+    opacity: 0.5 !important;
+}
+
+/* Keep text labels bold and normal color when checkbox is disabled */
+.checkbox-container:has(input[type="checkbox"]:disabled) {
+    cursor: not-allowed !important;
+    pointer-events: none !important;
+    opacity: 1 !important;
+    color: #2c3e50 !important;
+    font-weight: 600 !important;
+}
+
+.checkbox-container:has(input[type="checkbox"]:disabled):hover {
+    color: #2c3e50 !important;
+}
+
+/* Prevent interaction on disabled checkbox inputs */
+.checkbox-container input[type="checkbox"]:disabled {
+    cursor: not-allowed !important;
+    pointer-events: none !important;
+    opacity: 0.5 !important;
+}
+
+/* Gray out the checkmark for disabled checkboxes */
+.checkbox-container input[type="checkbox"]:disabled:checked {
+    background-color: #6c757d !important;
+    border-color: #6c757d !important;
+}
+
+.checkbox-container input[type="checkbox"]:disabled:checked::after {
+    color: #ffffff !important;
+}
+
+/* Frozen/Disabled Toggle Switches - Gray only the toggle, keep it hidden */
+.switch input[type="checkbox"]:disabled {
+    opacity: 0 !important; /* Keep the input completely hidden */
+    cursor: not-allowed !important;
+    pointer-events: none !important;
+    width: 0 !important;
+    height: 0 !important;
+}
+
+.switch input[type="checkbox"]:disabled + .slider {
+    opacity: 0.5 !important;
+    cursor: not-allowed !important;
+    pointer-events: none !important;
+    background-color: #95a5a6 !important; /* Gray color for disabled toggles */
+}
+
+.switch input[type="checkbox"]:disabled:checked + .slider {
+    background-color: #95a5a6 !important; /* Gray color even when checked */
+}
+
+.switch input[type="checkbox"]:disabled:not(:checked) + .slider {
+    background-color: #bdc3c7 !important; /* Lighter gray when unchecked */
+}
+
+.switch:has(input[type="checkbox"]:disabled) {
+    cursor: not-allowed !important;
+    pointer-events: none !important;
+    opacity: 1 !important; /* Keep switch container visible */
+}
+
+.switch:has(input[type="checkbox"]:disabled) .slider {
+    cursor: not-allowed !important;
+    pointer-events: none !important;
+}
+
+/* Ensure disabled switch input stays completely hidden */
+.switch input[type="checkbox"]:disabled {
+    position: absolute !important;
+    opacity: 0 !important;
+    width: 0 !important;
+    height: 0 !important;
+    margin: 0 !important;
+    padding: 0 !important;
+}
+
+/* Docking Section Collapsible Styles */
+#docking-section.collapsed .section-description,
+#docking-section.collapsed .custom-plumed-section {
+    max-height: 0;
+    opacity: 0;
+    margin-top: 0;
+    margin-bottom: 0;
+    padding-top: 0;
+    padding-bottom: 0;
+    overflow: hidden;
+    transition: max-height 0.4s ease, opacity 0.3s ease, margin 0.3s ease, padding 0.3s ease;
+}
+
+#docking-section.collapsed .plumed-toggle-header {
+    margin-bottom: 0;
+}
+
+.docking-box-row {
+    display: flex;
+    gap: 10px;
+    margin-bottom: 10px;
+}
+
+.docking-box-row .form-group {
+    flex: 1;
+}
+
+.docking-setup-entry {
+    margin-bottom: 15px;
+    padding: 10px;
+    background: white;
+    border-radius: 5px;
+    border: 1px solid #dee2e6;
+}
+
+.docking-setup-header {
+    display: flex;
+    justify-content: space-between;
+    align-items: center;
+    margin-bottom: 10px;
+}
+
+.docking-setup-chains {
+    font-size: 0.9em;
+    color: #6c757d;
+}
+
+/* Docking Ligand Selection Row Styles */
+.docking-ligand-row {
+    transition: all 0.2s ease;
+}
+
+.docking-ligand-row:hover {
+    background: #e9ecef !important;
+    border-color: #6f42c1 !important;
+}
+
+.docking-ligand-row .checkbox-container {
+    display: flex;
+    align-items: center;
+    gap: 8px;
+}
+
+/* Docking Box Controls Compact Layout */
+#docking-setup-list {
+    display: flex;
+    flex-wrap: wrap;
+    gap: 15px;
+}
+
+.docking-setup-entry {
+    transition: all 0.2s ease;
+}
+
+.docking-setup-entry:hover {
+    border-color: #6f42c1 !important;
+    box-shadow: 0 2px 8px rgba(111, 66, 193, 0.15);
+}
+
+.docking-setup-entry input[type="number"] {
+    transition: border-color 0.2s ease;
+}
+
+.docking-setup-entry input[type="number"]:focus {
+    border-color: #6f42c1;
+    outline: none;
+    box-shadow: 0 0 0 2px rgba(111, 66, 193, 0.1);
+}
+
+/* Small checkmarks for chain selection */
+.docking-ligand-row .checkmark {
+    width: 16px !important;
+    height: 16px !important;
+}
+
+.docking-ligand-row .checkmark:after {
+    left: 5px !important;
+    top: 2px !important;
+    width: 4px !important;
+    height: 8px !important;
+}
+
+
+/* Docking Setup Collapsible Section */
+.docking-setup-collapsible {
+    transition: all 0.3s ease;
+}
+
+.docking-setup-header {
+    user-select: none;
+    transition: background 0.2s ease;
+}
+
+.docking-setup-header:hover {
+    background: linear-gradient(135deg, #5a31a8 0%, #7d4bc7 100%) !important;
+}
+
+.docking-setup-content {
+    transition: all 0.3s ease;
+}
+
+#docking-setup-toggle-icon {
+    transition: transform 0.3s ease;
+}
+
+/* Docking Poses Viewer Styles */
+.docking-ligand-tabs {
+    display: flex;
+    gap: 8px;
+    margin-bottom: 15px;
+    flex-wrap: wrap;
+}
+
+.docking-ligand-tab {
+    padding: 8px 16px;
+    border: 2px solid #dee2e6;
+    border-radius: 6px;
+    background: #f8f9fa;
+    cursor: pointer;
+    font-weight: 500;
+    transition: all 0.2s ease;
+    display: flex;
+    align-items: center;
+    gap: 8px;
+}
+
+.docking-ligand-tab:hover {
+    border-color: #6f42c1;
+    background: #f3e8ff;
+}
+
+.docking-ligand-tab.active {
+    border-color: #6f42c1;
+    background: linear-gradient(135deg, #6f42c1 0%, #9b59b6 100%);
+    color: white;
+}
+
+.docking-ligand-tab .ligand-color-dot {
+    width: 12px;
+    height: 12px;
+    border-radius: 50%;
+    display: inline-block;
+}
+
+.docking-poses-viewer-wrapper {
+    position: relative;
+    margin-bottom: 15px;
+    max-width: 700px;
+    margin-left: auto;
+    margin-right: auto;
+}
+
+.docking-poses-viewer {
+    width: 100%;
+    max-width: 700px;
+    height: 500px;
+    background: #fff;
+    border-radius: 5px;
+    border: 2px solid #6f42c1;
+    overflow: hidden;
+    margin: 0 auto;
+}
+
+.pose-nav-controls {
+    position: absolute;
+    bottom: 0;
+    left: 0;
+    right: 0;
+    display: flex;
+    justify-content: center;
+    align-items: center;
+    gap: 20px;
+    padding: 15px;
+    background: linear-gradient(to top, rgba(255,255,255,0.95) 0%, rgba(255,255,255,0) 100%);
+    border-radius: 0 0 5px 5px;
+}
+
+.pose-nav-btn {
+    width: 50px;
+    height: 50px;
+    border-radius: 50%;
+    border: 2px solid #6f42c1;
+    background: white;
+    color: #6f42c1;
+    cursor: pointer;
+    transition: all 0.2s ease;
+    display: flex;
+    align-items: center;
+    justify-content: center;
+    font-size: 1.2rem;
+    box-shadow: 0 2px 8px rgba(0,0,0,0.15);
+}
+
+.pose-nav-btn:hover:not(:disabled) {
+    background: #6f42c1;
+    border-color: #6f42c1;
+    color: white;
+    transform: scale(1.1);
+}
+
+.pose-nav-btn:disabled {
+    opacity: 0.3;
+    cursor: not-allowed;
+}
+
+.pose-info-display {
+    text-align: center;
+    min-width: 200px;
+}
+
+.pose-mode-label {
+    font-size: 1.1rem;
+    font-weight: 600;
+    color: #333;
+}
+
+.pose-energy-label {
+    font-size: 0.95rem;
+    color: #28a745;
+    font-weight: 500;
+}
+
+.pose-color-legend {
+    display: flex;
+    gap: 20px;
+    justify-content: center;
+    margin-top: 8px;
+    font-size: 0.85rem;
+}
+
+.pose-color-legend span {
+    display: flex;
+    align-items: center;
+    gap: 6px;
+    color: #555;
+}
+
+.legend-dot {
+    width: 12px;
+    height: 12px;
+    border-radius: 50%;
+    display: inline-block;
+}
+
+.legend-dot.original {
+    background: #00ff00;
+}
+
+.legend-dot.docked {
+    background: #ff6b6b;
+}
+
+.docking-poses-selection {
+    background: #f8f9fa;
+    border-radius: 8px;
+    padding: 15px;
+    border: 1px solid #dee2e6;
+}
+
+.docking-poses-selection h5 {
+    margin-bottom: 10px;
+    color: #495057;
+    font-size: 0.95rem;
+}
+
+.pose-selection-row {
+    display: flex;
+    align-items: center;
+    gap: 15px;
+    padding: 10px;
+    background: white;
+    border-radius: 6px;
+    margin-bottom: 8px;
+    border: 1px solid #e9ecef;
+}
+
+.pose-selection-row:last-child {
+    margin-bottom: 0;
+}
+
+.pose-selection-label {
+    font-weight: 500;
+    min-width: 100px;
+}
+
+.pose-selection-options {
+    display: flex;
+    gap: 15px;
+    flex-wrap: wrap;
+}
+
+.pose-selection-option {
+    display: flex;
+    align-items: center;
+    gap: 6px;
+    cursor: pointer;
+    padding: 4px 8px;
+    border-radius: 4px;
+    transition: background 0.2s ease;
+}
+
+.pose-selection-option:hover {
+    background: #e9ecef;
+}
+
+.pose-selection-option input[type="radio"] {
+    accent-color: #6f42c1;
+}
+
+.pose-selection-option.selected {
+    background: #f3e8ff;
+    border: 1px solid #6f42c1;
+}
+
+.pose-selection-energy {
+    font-size: 0.85rem;
+    color: #28a745;
+    font-weight: 500;
+}

ambermdflow/docking.py

@@ -0,0 +1,54 @@
+# Step 1 obabel -i pdb ../4_ligands_corrected_1.pdb -o sdf -O ligand.sdf
+
+# Step 2 Run tleap on 1_protein_no_hydrogens.pdb to protonate and add hydrogen to the pdb file 
+# leap file content:
+# source leaprc.protein.ff14SB
+# protein = loadpdb 1_protein_no_hydrogens.pdb
+# savepdb protein protein.pdb
+# quit
+
+# Step 3 pdb4amber -i receptor.pdb -o receptor_fixed.pdb  run this command on protein to add element names 
+
+# Step 4 mk_prepare_ligand.py -i ligand.sdf -o ligand.pdbqt run this command on ligand to get pdbqt file for selected ligand
+
+# Step 4 mk_prepare_receptor.py -i receptor.pdb -o receptor -p   run this command on protein to get pdbqt file for selected protein chain
+
+# Now we are ready to run the docking 
+
+# find the center of the ligand
+# run this script 
+#from MDAnalysis import Universe
+#import numpy as np
+#
+#u = Universe("../output/4_ligands_corrected_1.pdb")
+#
+## replace 'LIG' with your ligand residue name
+#ligand = u.select_atoms("all")
+#coords = ligand.positions
+#
+## compute center of ligand
+#center = coords.mean(axis=0)
+#print("Center of ligand:", center)
+
+#then run this vina script 
+#vina \
+#  --receptor receptor_ready.pdbqt \
+#  --ligand ligand_1.pdbqt \
+#  --center_x 34.3124 \
+#  --center_y 4.95463 \
+#  --center_z 1.774217 \
+#  --size_x 18 \
+#  --size_y 18 \
+#  --size_z 18 \
+#  --out ligand_1_docked.pdbqt \
+#  --log ligand_1_docked.log
+
+#vina_split --input ligand_1_docked.pdbqt --ligand ligand_1_mode
+
+#Now we need to turn back pdbqt file to pdb file for ligand 
+#run this command to do that obabel ligand_1_mode1.pdbqt -O ligand_1_mode1.pdb -p 7.4 
+#now we need to add remaining hydrogens in it using pymol. pymol command is h_add ligand_1_mode1.pdb
+
+#Now we need to make sure the residue name is correct like the name in the original ligand and then 
+#we need to rename the atoms names to give this ligand to antechamber like C1, N1, .. like the way '4_ligands_corrected_1.pdb' formated 
+#Now this ligand is ready to be used by antechambe to generate force field parameters

ambermdflow/docking_utils.py

@@ -0,0 +1,639 @@
+#!/usr/bin/env python3
+"""
+Docking Utilities for AmberMDFlow
+
+This module contains all the Python functions needed for the docking workflow:
+1. Compute ligand center
+2. Prepare receptor (tleap + pdb4amber + meeko)
+3. Prepare ligand (obabel + meeko)
+4. Run Vina docking
+5. Split docked poses (vina_split)
+6. Convert poses to PDB (obabel)
+7. Sanitize docked poses for use in MD workflow
+
+Usage:
+    from docking_utils import (
+        compute_ligand_center,
+        prepare_receptor,
+        prepare_ligand,
+        run_vina_docking,
+        split_docked_poses,
+        convert_pdbqt_to_pdb,
+        sanitize_docked_pose
+    )
+"""
+
+import subprocess
+from pathlib import Path
+import logging
+
+logger = logging.getLogger(__name__)
+
+
+def compute_ligand_center(pdb_path: str) -> tuple:
+    """
+    Compute the geometric center of all atoms in a ligand PDB file.
+    
+    Args:
+        pdb_path: Path to the ligand PDB file
+        
+    Returns:
+        Tuple of (x, y, z) center coordinates
+    """
+    try:
+        import MDAnalysis as mda
+        import numpy as np
+    except ImportError as e:
+        raise RuntimeError(
+            "MDAnalysis and NumPy are required. Install with: "
+            "conda install -c conda-forge mdanalysis numpy"
+        ) from e
+    
+    pdb_path = Path(pdb_path)
+    if not pdb_path.exists():
+        raise FileNotFoundError(f"Ligand file not found: {pdb_path}")
+    
+    u = mda.Universe(str(pdb_path))
+    if u.atoms.n_atoms == 0:
+        raise ValueError(f"No atoms found in ligand file {pdb_path}")
+    
+    coords = u.atoms.positions.astype(float)
+    center = coords.mean(axis=0)
+    
+    logger.info(f"Ligand center for {pdb_path.name}: ({center[0]:.3f}, {center[1]:.3f}, {center[2]:.3f})")
+    return float(center[0]), float(center[1]), float(center[2])
+
+
+def prepare_receptor(protein_pdb: str, output_dir: str) -> tuple:
+    """
+    Prepare receptor for docking:
+    1. Run tleap to add hydrogens
+    2. Run pdb4amber to fix element names
+    3. Run mk_prepare_receptor.py to create PDBQT
+    
+    Args:
+        protein_pdb: Path to protein PDB file (typically 1_protein_no_hydrogens.pdb)
+        output_dir: Directory to store output files
+        
+    Returns:
+        Tuple of (receptor_fixed_pdb_path, receptor_pdbqt_path)
+    """
+    protein_pdb = Path(protein_pdb).resolve()
+    output_dir = Path(output_dir)
+    output_dir.mkdir(parents=True, exist_ok=True)
+    
+    if not protein_pdb.exists():
+        raise FileNotFoundError(f"Protein PDB not found: {protein_pdb}")
+    
+    # Step 1: tleap - add hydrogens
+    tleap_in = output_dir / "prepare_receptor.in"
+    receptor_pdb = output_dir / "receptor.pdb"
+    
+    if not receptor_pdb.exists():
+        logger.info("Step 1: Running tleap to add hydrogens to protein...")
+        with open(tleap_in, "w") as f:
+            f.write("source leaprc.protein.ff14SB\n")
+            f.write(f"protein = loadpdb {protein_pdb}\n")
+            f.write("savepdb protein receptor.pdb\n")
+            f.write("quit\n")
+        
+        result = subprocess.run(
+            ["tleap", "-f", tleap_in.name],
+            cwd=output_dir,
+            capture_output=True,
+            text=True,
+        )
+        if result.returncode != 0 or not receptor_pdb.exists():
+            raise RuntimeError(
+                f"tleap failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+            )
+        logger.info(f"  Created: {receptor_pdb}")
+    
+    # Step 2: pdb4amber - fix element names
+    receptor_fixed = output_dir / "receptor_fixed.pdb"
+    
+    if not receptor_fixed.exists():
+        logger.info("Step 2: Running pdb4amber to add element names...")
+        result = subprocess.run(
+            ["pdb4amber", "-i", str(receptor_pdb), "-o", str(receptor_fixed)],
+            capture_output=True,
+            text=True,
+        )
+        if result.returncode != 0 or not receptor_fixed.exists():
+            raise RuntimeError(
+                f"pdb4amber failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+            )
+        logger.info(f"  Created: {receptor_fixed}")
+    
+    # Step 3: Meeko receptor preparation
+    receptor_pdbqt = output_dir / "receptor.pdbqt"
+    
+    if not receptor_pdbqt.exists():
+        logger.info("Step 3: Running mk_prepare_receptor.py to create PDBQT...")
+        result = subprocess.run(
+            ["mk_prepare_receptor.py", "-i", str(receptor_fixed), "-o", "receptor", "-p"],
+            cwd=output_dir,
+            capture_output=True,
+            text=True,
+        )
+        if result.returncode != 0 or not receptor_pdbqt.exists():
+            raise RuntimeError(
+                f"mk_prepare_receptor.py failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+            )
+        logger.info(f"  Created: {receptor_pdbqt}")
+    
+    return str(receptor_fixed), str(receptor_pdbqt)
+
+
+def prepare_ligand(ligand_pdb: str, output_dir: str, ligand_index: int = 1) -> str:
+    """
+    Prepare ligand for docking:
+    1. Convert PDB to SDF using obabel
+    2. Convert SDF to PDBQT using mk_prepare_ligand.py
+    
+    Args:
+        ligand_pdb: Path to ligand PDB file
+        output_dir: Directory to store output files
+        ligand_index: Index number for naming output files
+        
+    Returns:
+        Path to ligand PDBQT file
+    """
+    ligand_pdb = Path(ligand_pdb)
+    output_dir = Path(output_dir)
+    output_dir.mkdir(parents=True, exist_ok=True)
+    
+    if not ligand_pdb.exists():
+        raise FileNotFoundError(f"Ligand PDB not found: {ligand_pdb}")
+    
+    # Step 1: obabel PDB -> SDF
+    sdf_path = output_dir / f"ligand_{ligand_index}.sdf"
+    
+    logger.info(f"Step 1: Converting ligand {ligand_index} PDB to SDF...")
+    result = subprocess.run(
+        ["obabel", "-i", "pdb", str(ligand_pdb), "-o", "sdf", "-O", str(sdf_path)],
+        capture_output=True,
+        text=True,
+    )
+    if result.returncode != 0 or not sdf_path.exists():
+        raise RuntimeError(
+            f"obabel failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+        )
+    logger.info(f"  Created: {sdf_path}")
+    
+    # Step 2: Meeko ligand preparation -> PDBQT
+    pdbqt_path = output_dir / f"ligand_{ligand_index}.pdbqt"
+    
+    logger.info(f"Step 2: Converting ligand {ligand_index} SDF to PDBQT...")
+    result = subprocess.run(
+        ["mk_prepare_ligand.py", "-i", str(sdf_path), "-o", str(pdbqt_path)],
+        capture_output=True,
+        text=True,
+    )
+    if result.returncode != 0 or not pdbqt_path.exists():
+        raise RuntimeError(
+            f"mk_prepare_ligand.py failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+        )
+    logger.info(f"  Created: {pdbqt_path}")
+    
+    return str(pdbqt_path)
+
+
+def run_vina_docking(
+    receptor_pdbqt: str,
+    ligand_pdbqt: str,
+    center_x: float,
+    center_y: float,
+    center_z: float,
+    size_x: float = 18.0,
+    size_y: float = 18.0,
+    size_z: float = 18.0,
+    output_dir: str = None,
+    ligand_index: int = 1,
+    exhaustiveness: int = 8,
+    num_modes: int = 9,
+) -> tuple:
+    """
+    Run AutoDock Vina docking.
+    
+    Args:
+        receptor_pdbqt: Path to receptor PDBQT file
+        ligand_pdbqt: Path to ligand PDBQT file
+        center_x, center_y, center_z: Box center coordinates (Angstroms)
+        size_x, size_y, size_z: Box dimensions (Angstroms)
+        output_dir: Directory for output files (default: same as ligand)
+        ligand_index: Index for naming output files
+        exhaustiveness: Search exhaustiveness (default: 8)
+        num_modes: Maximum number of binding modes (default: 9)
+        
+    Returns:
+        Tuple of (docked_pdbqt_path, log_file_path)
+    """
+    ligand_pdbqt = Path(ligand_pdbqt)
+    output_dir = Path(output_dir) if output_dir else ligand_pdbqt.parent
+    
+    docked_pdbqt = output_dir / f"ligand_{ligand_index}_docked.pdbqt"
+    log_file = output_dir / f"ligand_{ligand_index}_docked.log"
+    
+    logger.info(f"Running Vina docking for ligand {ligand_index}...")
+    logger.info(f"  Center: ({center_x:.3f}, {center_y:.3f}, {center_z:.3f})")
+    logger.info(f"  Size: ({size_x:.1f}, {size_y:.1f}, {size_z:.1f})")
+    
+    cmd = [
+        "vina",
+        "--receptor", str(receptor_pdbqt),
+        "--ligand", str(ligand_pdbqt),
+        "--center_x", str(center_x),
+        "--center_y", str(center_y),
+        "--center_z", str(center_z),
+        "--size_x", str(size_x),
+        "--size_y", str(size_y),
+        "--size_z", str(size_z),
+        "--out", str(docked_pdbqt),
+        "--log", str(log_file),
+        "--exhaustiveness", str(exhaustiveness),
+        "--num_modes", str(num_modes),
+    ]
+    
+    result = subprocess.run(cmd, capture_output=True, text=True)
+    
+    if result.returncode != 0 or not docked_pdbqt.exists():
+        raise RuntimeError(
+            f"Vina docking failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+        )
+    
+    logger.info(f"  Created: {docked_pdbqt}")
+    logger.info(f"  Log: {log_file}")
+    
+    return str(docked_pdbqt), str(log_file)
+
+
+def parse_vina_log(log_path: str) -> list:
+    """
+    Parse Vina log file to extract binding energies for each mode.
+    
+    Args:
+        log_path: Path to Vina log file
+        
+    Returns:
+        List of dicts with 'mode', 'affinity', 'rmsd_lb', 'rmsd_ub' for each pose
+    """
+    log_path = Path(log_path)
+    if not log_path.exists():
+        return []
+    
+    energies = []
+    in_results = False
+    
+    with open(log_path, "r") as f:
+        for line in f:
+            line = line.strip()
+            if "-----+------------+----------+----------" in line:
+                in_results = True
+                continue
+            if in_results and line and line[0].isdigit():
+                parts = line.split()
+                if len(parts) >= 4:
+                    try:
+                        energies.append({
+                            'mode': int(parts[0]),
+                            'affinity': float(parts[1]),
+                            'rmsd_lb': float(parts[2]),
+                            'rmsd_ub': float(parts[3]),
+                        })
+                    except (ValueError, IndexError):
+                        continue
+            elif in_results and not line:
+                break
+    
+    return energies
+
+
+def split_docked_poses(docked_pdbqt: str, output_prefix: str = None) -> list:
+    """
+    Split docked PDBQT into individual pose files using vina_split.
+    
+    Args:
+        docked_pdbqt: Path to docked PDBQT file with multiple poses
+        output_prefix: Prefix for output files (default: derived from input)
+        
+    Returns:
+        List of paths to individual pose PDBQT files
+    """
+    docked_pdbqt = Path(docked_pdbqt)
+    if not docked_pdbqt.exists():
+        raise FileNotFoundError(f"Docked PDBQT not found: {docked_pdbqt}")
+    
+    output_dir = docked_pdbqt.parent
+    if output_prefix is None:
+        output_prefix = docked_pdbqt.stem.replace("_docked", "_mode")
+    
+    logger.info(f"Splitting docked poses from {docked_pdbqt.name}...")
+    
+    result = subprocess.run(
+        ["vina_split", "--input", str(docked_pdbqt), "--ligand", output_prefix],
+        cwd=output_dir,
+        capture_output=True,
+        text=True,
+    )
+    
+    if result.returncode != 0:
+        raise RuntimeError(
+            f"vina_split failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+        )
+    
+    # Find all generated mode files
+    pose_files = sorted(output_dir.glob(f"{output_prefix}*.pdbqt"))
+    logger.info(f"  Split into {len(pose_files)} pose files")
+    
+    return [str(f) for f in pose_files]
+
+
+def convert_pdbqt_to_pdb(pdbqt_path: str, ph: float = 7.4) -> str:
+    """
+    Convert PDBQT file to PDB using obabel.
+    
+    Args:
+        pdbqt_path: Path to PDBQT file
+        ph: pH for protonation (default: 7.4)
+        
+    Returns:
+        Path to output PDB file
+    """
+    pdbqt_path = Path(pdbqt_path)
+    if not pdbqt_path.exists():
+        raise FileNotFoundError(f"PDBQT file not found: {pdbqt_path}")
+    
+    pdb_path = pdbqt_path.with_suffix(".pdb")
+    
+    logger.info(f"Converting {pdbqt_path.name} to PDB...")
+    
+    result = subprocess.run(
+        ["obabel", str(pdbqt_path), "-O", str(pdb_path), "-p", str(ph)],
+        capture_output=True,
+        text=True,
+    )
+    
+    if result.returncode != 0 or not pdb_path.exists():
+        raise RuntimeError(
+            f"obabel conversion failed:\nSTDOUT:\n{result.stdout}\nSTDERR:\n{result.stderr}"
+        )
+    
+    logger.info(f"  Created: {pdb_path}")
+    return str(pdb_path)
+
+
+def sanitize_docked_pose(original_ligand: str, pose_pdb: str) -> str:
+    """
+    Sanitize a docked pose PDB to match the original ligand format:
+    - Restore residue name, chain ID, and residue number from original
+    - Convert ATOM to HETATM
+    - Rename atoms to match original format (C1, N1, etc.)
+    - Remove CONECT/MASTER records
+    
+    Args:
+        original_ligand: Path to original ligand PDB file
+        pose_pdb: Path to docked pose PDB file
+        
+    Returns:
+        Path to sanitized pose PDB (same as pose_pdb, modified in place)
+    """
+    original_ligand = Path(original_ligand)
+    pose_pdb = Path(pose_pdb)
+    
+    if not original_ligand.exists():
+        raise FileNotFoundError(f"Original ligand not found: {original_ligand}")
+    if not pose_pdb.exists():
+        raise FileNotFoundError(f"Pose PDB not found: {pose_pdb}")
+    
+    # Extract residue info from original ligand
+    resname = "LIG"
+    chain = "X"
+    resnum = 1
+    
+    with open(original_ligand, "r") as f:
+        for line in f:
+            if line.startswith(("ATOM", "HETATM")):
+                resname = line[17:20].strip() or "LIG"
+                chain = line[21] if len(line) > 21 and line[21].strip() else "X"
+                try:
+                    resnum = int(line[22:26].strip())
+                except ValueError:
+                    resnum = 1
+                break
+    
+    logger.info(f"Sanitizing pose with resname={resname}, chain={chain}, resnum={resnum}")
+    
+    # Process pose PDB
+    new_lines = []
+    atom_counter = 0
+    element_counts = {}
+    
+    with open(pose_pdb, "r") as f:
+        for line in f:
+            if line.startswith(("CONECT", "MASTER")):
+                continue
+            if line.startswith(("ATOM", "HETATM")):
+                atom_counter += 1
+                
+                # Extract element from line or atom name
+                element = line[76:78].strip() if len(line) > 77 else ""
+                if not element:
+                    # Try to get from atom name
+                    atom_name = line[12:16].strip()
+                    element = ''.join(c for c in atom_name if c.isalpha())[:2]
+                    if len(element) > 1:
+                        element = element[0].upper() + element[1].lower()
+                
+                if not element:
+                    element = "C"  # Default fallback
+                
+                # Generate new atom name (C1, C2, N1, etc.)
+                element_counts[element] = element_counts.get(element, 0) + 1
+                new_atom_name = f"{element}{element_counts[element]}"
+                new_atom_name = f"{new_atom_name:<4}"  # Left-justified, 4 chars
+                
+                # Build new line as HETATM
+                new_line = (
+                    f"HETATM{atom_counter:5d} {new_atom_name}"
+                    f"{resname:>3s} {chain}{resnum:4d}    "
+                    f"{line[30:54]}"  # Coordinates
+                    f"{line[54:66] if len(line) > 54 else '  1.00  0.00'}"  # Occupancy, B-factor
+                    f"          {element:>2s}\n"
+                )
+                new_lines.append(new_line)
+            elif line.startswith("END"):
+                new_lines.append("END\n")
+    
+    # Write sanitized file
+    with open(pose_pdb, "w") as f:
+        f.writelines(new_lines)
+    
+    logger.info(f"  Sanitized: {pose_pdb}")
+    return str(pose_pdb)
+
+
+def run_full_docking_workflow(
+    protein_pdb: str,
+    ligand_pdbs: list,
+    output_dir: str,
+    box_configs: dict = None,
+) -> dict:
+    """
+    Run the complete docking workflow for multiple ligands.
+    
+    Args:
+        protein_pdb: Path to protein PDB file (1_protein_no_hydrogens.pdb)
+        ligand_pdbs: List of paths to ligand PDB files
+        output_dir: Base output directory for docking results
+        box_configs: Optional dict of {ligand_index: {'center': (x,y,z), 'size': (sx,sy,sz)}}
+        
+    Returns:
+        Dict with results for each ligand including poses and energies
+    """
+    output_dir = Path(output_dir)
+    output_dir.mkdir(parents=True, exist_ok=True)
+    box_configs = box_configs or {}
+    
+    results = {
+        'success': True,
+        'ligands': [],
+        'warnings': [],
+        'errors': [],
+    }
+    
+    # Step 1: Prepare receptor (only once for all ligands)
+    logger.info("=" * 60)
+    logger.info("STEP 1: Preparing receptor for docking")
+    logger.info("=" * 60)
+    
+    try:
+        receptor_fixed, receptor_pdbqt = prepare_receptor(protein_pdb, str(output_dir))
+    except Exception as e:
+        results['success'] = False
+        results['errors'].append(f"Receptor preparation failed: {str(e)}")
+        return results
+    
+    # Step 2: Process each ligand
+    for idx, ligand_pdb in enumerate(ligand_pdbs, start=1):
+        ligand_pdb = Path(ligand_pdb)
+        logger.info("")
+        logger.info("=" * 60)
+        logger.info(f"STEP 2.{idx}: Processing ligand {idx}: {ligand_pdb.name}")
+        logger.info("=" * 60)
+        
+        lig_dir = output_dir / f"ligand_{idx}"
+        lig_dir.mkdir(parents=True, exist_ok=True)
+        
+        ligand_result = {
+            'index': idx,
+            'original_file': str(ligand_pdb),
+            'poses': [],
+            'energies': [],
+            'success': True,
+        }
+        
+        try:
+            # Copy original ligand for reference
+            original_copy = lig_dir / "original_ligand.pdb"
+            if not original_copy.exists():
+                original_copy.write_text(ligand_pdb.read_text())
+            
+            # Prepare ligand PDBQT
+            ligand_pdbqt = prepare_ligand(str(ligand_pdb), str(lig_dir), idx)
+            
+            # Get box configuration
+            cfg = box_configs.get(idx, {})
+            center = cfg.get('center')
+            size = cfg.get('size', (18.0, 18.0, 18.0))
+            
+            if center is None:
+                # Compute center from ligand
+                cx, cy, cz = compute_ligand_center(str(ligand_pdb))
+            else:
+                cx, cy, cz = center
+            
+            sx, sy, sz = size
+            
+            # Run Vina docking
+            docked_pdbqt, log_file = run_vina_docking(
+                receptor_pdbqt, ligand_pdbqt,
+                cx, cy, cz, sx, sy, sz,
+                str(lig_dir), idx
+            )
+            
+            # Parse binding energies
+            energies = parse_vina_log(log_file)
+            ligand_result['energies'] = energies
+            
+            # Split poses
+            pose_pdbqts = split_docked_poses(docked_pdbqt)
+            
+            # Convert each pose to PDB and sanitize
+            for pose_pdbqt in pose_pdbqts:
+                pose_pdb = convert_pdbqt_to_pdb(pose_pdbqt)
+                sanitize_docked_pose(str(original_copy), pose_pdb)
+                ligand_result['poses'].append(pose_pdb)
+            
+        except Exception as e:
+            ligand_result['success'] = False
+            ligand_result['error'] = str(e)
+            results['errors'].append(f"Ligand {idx}: {str(e)}")
+            logger.error(f"Error processing ligand {idx}: {e}")
+        
+        results['ligands'].append(ligand_result)
+    
+    # Check overall success
+    results['success'] = all(lig['success'] for lig in results['ligands'])
+    
+    logger.info("")
+    logger.info("=" * 60)
+    logger.info("DOCKING WORKFLOW COMPLETE")
+    logger.info("=" * 60)
+    
+    return results
+
+
+# Example usage / CLI interface
+if __name__ == "__main__":
+    import argparse
+    
+    logging.basicConfig(level=logging.INFO, format='%(message)s')
+    
+    parser = argparse.ArgumentParser(description="Run AutoDock Vina docking workflow")
+    parser.add_argument("--protein", required=True, help="Path to protein PDB file")
+    parser.add_argument("--ligands", nargs="+", required=True, help="Paths to ligand PDB files")
+    parser.add_argument("--output", required=True, help="Output directory")
+    parser.add_argument("--center", nargs=3, type=float, help="Box center (x y z)")
+    parser.add_argument("--size", nargs=3, type=float, default=[18, 18, 18], help="Box size (x y z)")
+    
+    args = parser.parse_args()
+    
+    box_configs = {}
+    if args.center:
+        for i in range(1, len(args.ligands) + 1):
+            box_configs[i] = {
+                'center': tuple(args.center),
+                'size': tuple(args.size),
+            }
+    
+    results = run_full_docking_workflow(
+        args.protein,
+        args.ligands,
+        args.output,
+        box_configs
+    )
+    
+    print("\n" + "=" * 60)
+    print("RESULTS SUMMARY")
+    print("=" * 60)
+    print(f"Overall success: {results['success']}")
+    for lig in results['ligands']:
+        print(f"\nLigand {lig['index']}:")
+        print(f"  Success: {lig['success']}")
+        if lig['success']:
+            print(f"  Poses generated: {len(lig['poses'])}")
+            if lig['energies']:
+                print(f"  Best binding energy: {lig['energies'][0]['affinity']} kcal/mol")
+        else:
+            print(f"  Error: {lig.get('error', 'Unknown')}")

ambermdflow/html/index.html

@@ -0,0 +1,1145 @@
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <meta charset="UTF-8">
+    <meta name="viewport" content="width=device-width, initial-scale=1.0">
+    <title>MD Simulation Pipeline</title>
+    <link rel="stylesheet" href="../css/styles.css">
+    <link rel="stylesheet" href="../css/plumed.css">
+    <link href="https://cdnjs.cloudflare.com/ajax/libs/font-awesome/6.0.0/css/all.min.css" rel="stylesheet">
+    <!-- THREE.js (needed for docking box visualization) - using r95 to match NGL's bundled version -->
+    <script src="https://cdnjs.cloudflare.com/ajax/libs/three.js/r95/three.min.js"></script>
+    <!-- NGL 3D Molecular Viewer -->
+    <script src="https://unpkg.com/ngl@2.0.0-dev.35/dist/ngl.js"></script>
+</head>
+<body>
+    <div class="container">
+        <!-- Header -->
+        <header class="header">
+            <div class="header-content">
+                <h1><i class="fas fa-atom"></i> MD Simulation Pipeline</h1>
+                <p>Molecular Dynamics Simulation Setup and File Generation</p>
+            </div>
+        </header>
+
+        <!-- Navigation Tabs -->
+        <nav class="tab-navigation">
+            <button class="tab-button active" data-tab="protein-loading">
+                <i class="fas fa-upload"></i> Protein Loading
+            </button>
+            <button class="tab-button" data-tab="fill-missing">
+                <i class="fas fa-puzzle-piece"></i> Fill Missing Residues
+            </button>
+            <button class="tab-button" data-tab="structure-prep">
+                <i class="fas fa-tools"></i> Structure Preparation
+            </button>
+            <button class="tab-button" data-tab="simulation-params">
+                <i class="fas fa-cogs"></i> Simulation Parameters
+            </button>
+            <button class="tab-button" data-tab="simulation-steps">
+                <i class="fas fa-list-ol"></i> Simulation Steps
+            </button>
+            <button class="tab-button" data-tab="file-generation">
+                <i class="fas fa-file-download"></i> Generate Files
+            </button>
+            <button class="tab-button" data-tab="plumed">
+                <i class="fas fa-chart-line"></i> PLUMED
+            </button>
+        </nav>
+
+        <!-- Main Content -->
+        <main class="main-content">
+            <!-- Protein Loading Tab -->
+            <div id="protein-loading" class="tab-content active">
+                <div class="card">
+                    <h2><i class="fas fa-dna"></i> Protein Structure Input</h2>
+                    
+                    <div class="input-methods">
+                        <div class="method-option">
+                            <h3><i class="fas fa-file-upload"></i> Upload PDB File</h3>
+                            <div class="file-upload-area" id="file-upload-area">
+                                <i class="fas fa-cloud-upload-alt"></i>
+                                <p>Drag and drop your PDB file here or click to browse</p>
+                                <input type="file" id="pdb-file" accept=".pdb,.ent" style="display: none;">
+                                <button type="button" class="btn btn-secondary" id="choose-file-btn">
+                                    Choose File
+                                </button>
+                            </div>
+                            <div id="file-info" class="file-info" style="display: none;">
+                                <p><strong>Selected file:</strong> <span id="file-name"></span></p>
+                                <p><strong>Size:</strong> <span id="file-size"></span></p>
+                            </div>
+                        </div>
+
+                        <div class="divider">
+                            <span>OR</span>
+                        </div>
+
+                        <div class="method-option">
+                            <h3><i class="fas fa-database"></i> Fetch from PDB</h3>
+                            <div class="pdb-fetch">
+                                <div class="input-group">
+                                    <label for="pdb-id">PDB ID:</label>
+                                    <input type="text" id="pdb-id" placeholder="e.g., 1CRN, 1HTM" maxlength="4">
+                                    <button type="button" class="btn btn-primary" id="fetch-pdb">
+                                        <i class="fas fa-download"></i> Fetch
+                                    </button>
+                                </div>
+                                <div id="pdb-status" class="status-message"></div>
+                            </div>
+                        </div>
+                    </div>
+
+                    <div class="protein-preview" id="protein-preview" style="display: none;">
+                        <h3><i class="fas fa-eye"></i> Protein Preview</h3>
+                        <div class="preview-content">
+                            <div class="protein-info">
+                                <p><strong>Structure ID:</strong> <span id="structure-id"></span></p>
+                                <p><strong>Number of atoms (Protein):</strong> <span id="atom-count"></span></p>
+                                <p><strong>Chains:</strong> <span id="chain-info"></span></p>
+                                <p><strong>Residues:</strong> <span id="residue-count"></span></p>
+                                <p><strong>Water molecules:</strong> <span id="water-count"></span></p>
+                                <p><strong>Ions:</strong> <span id="ion-count"></span></p>
+                                <p><strong>Ligands:</strong> <span id="ligand-info"></span></p>
+                                <p><strong>HETATM entries:</strong> <span id="hetatm-count"></span></p>
+                            </div>
+                            <div class="protein-visualization">
+                                <div id="molecule-viewer" class="molecule-viewer">
+                                    <!-- 3D visualization will be added here -->
+                                    <div id="ngl-viewer" style="width: 100%; height: 100%; min-height: 300px;"></div>
+                                    <div id="viewer-controls" class="viewer-controls" style="display: none;">
+                                        <button class="btn btn-sm btn-secondary" onclick="mdPipeline.resetView()">
+                                            <i class="fas fa-home"></i> Reset View
+                                        </button>
+                                        <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleRepresentation()">
+                                            <i class="fas fa-eye"></i> <span id="style-text">Mixed View</span>
+                                        </button>
+                                        <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleSpin()">
+                                            <i class="fas fa-sync"></i> Spin
+                                        </button>
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+                    </div>
+                </div>
+            </div>
+
+            <!-- Fill Missing Residues Tab -->
+            <div id="fill-missing" class="tab-content">
+                <div class="card">
+                    <h2><i class="fas fa-puzzle-piece"></i> Fill Missing Residues</h2>
+                    <p class="card-description">
+                        Detect missing residues in the experimental structure using RCSB annotations and complete them
+                        with ESMFold. You can choose which chains to include in the completion.
+                    </p>
+                    <p class="form-text text-muted" style="margin-top: 6px; font-size: 0.9em;">
+                        <i class="fas fa-book"></i> If you use this workflow in your research, please cite: <a href="https://esmatlas.com/about" target="_blank" rel="noopener noreferrer">ESM Atlas</a>
+                    </p>
+
+                    <div class="prep-sections">
+                        <div class="prep-section">
+                            <h3><i class="fas fa-search"></i> Detect Missing Residues</h3>
+                            <button class="btn btn-primary" id="detect-missing-residues">
+                                <i class="fas fa-search"></i> Analyze Missing Residues
+                            </button>
+                            <div id="missing-status" class="status-message" style="margin-top: 10px;"></div>
+                        </div>
+
+                        <div class="prep-section" id="missing-chains-section" style="display: none;">
+                            <h3><i class="fas fa-link"></i> Select Chains for Completion</h3>
+                            <p class="option-description">
+                                Chains listed below have missing residues. Select which chains you want to rebuild with ESMFold.
+                            </p>
+                            <div id="missing-chains-list" class="multi-checkbox-group">
+                                <!-- Missing chains checkboxes will be rendered here -->
+                            </div>
+                            <small class="form-help">
+                                At least one chain must be selected to build a completed structure.
+                            </small>
+                        </div>
+                    </div>
+
+                    <div class="prep-section prep-section-fullwidth" id="trim-residues-section" style="display: none;">
+                        <h3><i class="fas fa-cut"></i> Trim Residues from Edges (Optional)</h3>
+                        <p class="option-description">
+                            Optionally trim residues from the N-terminal and/or C-terminal edges of selected chains. 
+                            This only removes residues from the edges, not from loops in between.
+                        </p>
+                        <div class="trim-info-box" id="trim-info-box-content">
+                            <i class="fas fa-info-circle"></i>
+                            <strong>Note:</strong> Only missing residues at the <strong>N-terminal edge</strong> (beginning of sequence) and <strong>C-terminal edge</strong> (end of sequence) can be trimmed. 
+                            Missing residues in internal loops (discontinuities in the middle of the sequence) cannot be trimmed using this tool and will be filled by ESMFold.
+                        </div>
+                        <div id="trim-residues-list" class="trim-residues-container">
+                            <!-- Trim controls for each chain will be rendered here -->
+                        </div>
+                        <button class="btn btn-secondary" id="apply-trim" style="margin-top: 15px;">
+                            <i class="fas fa-check"></i> Apply Trimming
+                        </button>
+                        <div id="trim-status" class="status-message" style="margin-top: 10px; display: none;"></div>
+                    </div>
+
+                    <!-- Chain Minimization Option -->
+                    <div class="prep-section" id="chain-minimization-section" style="display: none; margin-top: 20px; padding: 15px; background: #f8f9fa; border-radius: 5px; border: 1px solid #dee2e6;">
+                        <h3><i class="fas fa-compress-arrows-alt"></i> Energy Minimization (Optional)</h3>
+                        <div class="form-check" style="display: flex; align-items: center; gap: 10px; margin-top: 10px;">
+                            <input class="form-check-input" type="checkbox" id="minimize-chains-checkbox" style="width: 20px; height: 20px; cursor: pointer;">
+                            <label class="form-check-label" for="minimize-chains-checkbox" style="cursor: pointer; font-weight: 500; flex: 1;">
+                                <strong>Energy minimize ESMFold-generated chains</strong>
+                            </label>
+                        </div>
+                        <small class="form-text text-muted" style="display: block; margin-top: 8px; margin-left: 30px;">
+                            <i class="fas fa-info-circle"></i> Recommended: Minimization resolve structural clashes
+                        </small>
+                        <div id="minimization-chains-list" style="display: none; margin-top: 15px; margin-left: 30px;">
+                            <strong>Select chains to minimize:</strong>
+                            <div id="minimization-chains-checkboxes" class="multi-checkbox-group" style="margin-top: 10px;">
+                                <!-- Chain checkboxes will be populated here -->
+                            </div>
+                        </div>
+                    </div>
+
+                    <div class="prep-actions">
+                        <button class="btn btn-primary" id="build-complete-structure" disabled>
+                            <i class="fas fa-magic"></i> Build Completed Structure
+                        </button>
+                        <button class="btn btn-secondary" id="preview-completed-structure" disabled>
+                            <i class="fas fa-eye"></i> Preview Completed Structure
+                        </button>
+                        <button class="btn btn-secondary" id="preview-superimposed-structure" disabled>
+                            <i class="fas fa-layer-group"></i> View Superimposed Structures
+                        </button>
+                        <button class="btn btn-info" id="download-completed-structure" disabled>
+                            <i class="fas fa-download"></i> Download Completed PDB
+                        </button>
+                    </div>
+
+                    <div class="prep-status" id="missing-summary" style="display: none;">
+                        <h3><i class="fas fa-info-circle"></i> Missing Residues Summary</h3>
+                        <div class="status-content" id="missing-summary-content">
+                            <!-- Missing residues summary will be displayed here -->
+                        </div>
+                    </div>
+
+                    <div class="prep-actions" id="sequence-viewer-actions" style="display: none; margin-top: 1rem;">
+                        <button class="btn btn-secondary" id="view-protein-sequences">
+                            <i class="fas fa-dna"></i> View Protein Sequences
+                        </button>
+                    </div>
+
+                    <div class="prepared-structure-preview" id="sequence-viewer-section" style="display: none;">
+                        <h3><i class="fas fa-dna"></i> Protein Sequence Viewer</h3>
+                        <p class="card-description" style="margin-bottom: 15px;">
+                            View protein sequences for all chains. Chain colors match the structure visualization. Missing residues are shown in grey.
+                        </p>
+                        <div id="sequence-viewer-content" class="sequence-viewer-container">
+                            <!-- Sequence viewer will be rendered here -->
+                        </div>
+                    </div>
+
+                    <div class="prepared-structure-preview" id="completed-structure-preview" style="display: none;">
+                        <h3><i class="fas fa-eye"></i> Structure Comparison Preview</h3>
+                        <p class="card-description" style="margin-bottom: 15px;">
+                            Compare the completed structure (right) with the original crystal structure (left) to see the added missing residues.
+                        </p>
+                        <div class="preview-content" style="display: flex; justify-content: center; width: 100%; padding: 0;">
+                            <div class="structure-comparison-container" style="display: flex; gap: 20px; flex-direction: row; width: 100%; max-width: 1400px; align-items: flex-start; justify-content: center;">
+                                <!-- Original Structure Viewer -->
+                                <div class="comparison-viewer" style="flex: 0 1 48%; min-width: 450px; max-width: 48%;">
+                                    <h4 style="text-align: center; margin-bottom: 10px; font-size: 14px;">
+                                        <i class="fas fa-dna"></i> Original Crystal Structure
+                                    </h4>
+                                    <div id="original-molecule-viewer" class="molecule-viewer" style="border: 2px solid #007bff; border-radius: 5px; width: 100%; height: 500px; position: relative;">
+                                        <div id="original-ngl-viewer" style="width: 100%; height: 100%; position: absolute; top: 0; left: 0;"></div>
+                                        <div id="original-viewer-controls" class="viewer-controls" style="display: none; justify-content: center; position: relative; z-index: 10;">
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.resetOriginalView()">
+                                                <i class="fas fa-home"></i> Reset
+                                            </button>
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleOriginalRepresentation()">
+                                                <i class="fas fa-eye"></i> <span id="original-style-text">Mixed</span>
+                                            </button>
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleOriginalSpin()">
+                                                <i class="fas fa-sync"></i> Spin
+                                            </button>
+                                        </div>
+                                    </div>
+                                </div>
+                                
+                                <!-- Completed Structure Viewer -->
+                                <div class="comparison-viewer" style="flex: 0 1 48%; min-width: 450px; max-width: 48%;">
+                                    <h4 style="text-align: center; margin-bottom: 10px; font-size: 14px;">
+                                        <i class="fas fa-puzzle-piece"></i> Completed Structure
+                                    </h4>
+                                    <div id="completed-molecule-viewer" class="molecule-viewer" style="border: 2px solid #28a745; border-radius: 5px; width: 100%; height: 500px; position: relative;">
+                                        <div id="completed-ngl-viewer" style="width: 100%; height: 100%; position: absolute; top: 0; left: 0;"></div>
+                                        <div id="completed-viewer-controls" class="viewer-controls" style="display: none; justify-content: center; position: relative; z-index: 10;">
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.resetCompletedView()">
+                                                <i class="fas fa-home"></i> Reset
+                                            </button>
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleCompletedRepresentation()">
+                                                <i class="fas fa-eye"></i> <span id="completed-style-text">Mixed</span>
+                                            </button>
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleCompletedSpin()">
+                                                <i class="fas fa-sync"></i> Spin
+                                            </button>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+                    </div>
+
+                    <div class="prepared-structure-preview" id="superimposed-structure-preview" style="display: none;">
+                        <h3><i class="fas fa-layer-group"></i> Superimposed Structure View</h3>
+                        <p class="card-description" style="margin-bottom: 15px;">
+                            View both the original crystal structure (original colors) and completed structure (different chain colors) superimposed in the same viewer to see which residues were filled.
+                        </p>
+                        <div class="preview-content" style="display: flex; justify-content: center; width: 100%; padding: 0;">
+                            <div class="structure-comparison-container" style="width: 100%; max-width: 1400px;">
+                                <!-- Superimposed Structure Viewer -->
+                                <div class="comparison-viewer" style="width: 100%;">
+                                    <div style="display: flex; justify-content: space-between; align-items: center; margin-bottom: 10px;">
+                                        <div>
+                                            <span style="color: #007bff; font-weight: 600;"><i class="fas fa-dna"></i> Original Crystal Structure</span>
+                                            <span style="margin: 0 10px;">|</span>
+                                            <span style="color: #28a745; font-weight: 600;"><i class="fas fa-puzzle-piece"></i> Completed Structure</span>
+                                        </div>
+                                    </div>
+                                    <div id="superimposed-molecule-viewer" class="molecule-viewer" style="border: 2px solid #007bff; border-radius: 5px; width: 100%; height: 600px; position: relative;">
+                                        <div id="superimposed-ngl-viewer" style="width: 100%; height: 100%; position: absolute; top: 0; left: 0;"></div>
+                                        <div id="superimposed-viewer-controls" class="viewer-controls" style="display: none; gap: 10px;">
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.resetSuperimposedView()">
+                                                <i class="fas fa-home"></i> Reset
+                                            </button>
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleSuperimposedRepresentation()">
+                                                <i class="fas fa-eye"></i> <span id="superimposed-style-text">Cartoon</span>
+                                            </button>
+                                            <button class="btn btn-sm btn-secondary" onclick="mdPipeline.toggleSuperimposedSpin()">
+                                                <i class="fas fa-sync"></i> Spin
+                                            </button>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+                    </div>
+                </div>
+            </div>
+
+            <!-- Structure Preparation Tab -->
+            <div id="structure-prep" class="tab-content">
+                <div class="card">
+                    <h2><i class="fas fa-tools"></i> Structure Preparation for AMBER</h2>
+                    <p class="card-description">Prepare the protein structure for AMBER force field generation by cleaning and modifying the PDB file.</p>
+                    
+                    <div class="prep-sections">
+                        <div class="prep-section">
+                            <h3><i class="fas fa-trash"></i> Remove Components</h3>
+                            <div class="prep-options">
+                                <div class="prep-option">
+                                    <label class="checkbox-container">
+                                        <input type="checkbox" id="remove-water" checked disabled>
+                                        <span class="checkmark"></span>
+                                        Remove water molecules
+                                    </label>
+                                    <p class="option-description">Remove all water molecules (HOH, WAT, TIP3, etc.) from the structure</p>
+                                </div>
+                                
+                                <div class="prep-option">
+                                    <label class="checkbox-container">
+                                        <input type="checkbox" id="remove-ions" checked disabled>
+                                        <span class="checkmark"></span>
+                                        Remove ions
+                                    </label>
+                                    <p class="option-description">Remove all ions (Na+, Cl-, K+, Mg2+, etc.) from the structure</p>
+                                </div>
+                                
+                                <div class="prep-option">
+                                    <label class="checkbox-container">
+                                        <input type="checkbox" id="remove-hydrogens" checked disabled>
+                                        <span class="checkmark"></span>
+                                        Remove hydrogen atoms
+                                    </label>
+                                    <p class="option-description">Remove all hydrogen atoms from the protein structure</p>
+                                </div>
+                            </div>
+                        </div>
+
+                        <div class="prep-section">
+                            <h3><i class="fas fa-plus-circle"></i> Add Capping Groups and Select Protein  Chains</h3>
+                            <div class="prep-options">
+                                <div class="prep-option">
+                                    <label class="checkbox-container">
+                                        <input type="checkbox" id="add-nme" checked>
+                                        <span class="checkmark"></span>
+                                        Add NME group (C-terminal)
+                                    </label>
+                                    <p class="option-description">Add N-methyl amide (NME) group to C-terminal residues</p>
+                                </div>
+                                
+                                <div class="prep-option">
+                                    <label class="checkbox-container">
+                                        <input type="checkbox" id="add-ace" checked>
+                                        <span class="checkmark"></span>
+                                        Add ACE group (N-terminal)
+                                    </label>
+                                    <p class="option-description">Add acetyl (ACE) group to N-terminal residues</p>
+                                </div>
+
+                                <div class="form-group">
+                                    <label>Preserve Chains for FF Generation:</label>
+                                    <div id="chain-selection" class="multi-checkbox-group">
+                                        <!-- Chain checkboxes will be rendered here -->
+                                    </div>
+                                    <small class="form-help">Select one or more protein chains to include in preparation</small>
+                                </div>
+                            </div>
+                        </div>
+
+                        <div class="prep-section">
+                            <h3><i class="fas fa-pills"></i> Ligand Handling</h3>
+                            <div class="prep-options">
+                                <div class="prep-option">
+                                    <label class="checkbox-container">
+                                        <input type="checkbox" id="preserve-ligands">
+                                        <span class="checkmark"></span>
+                                        Preserve ligands
+                                    </label>
+                                    <p class="option-description">Keep ligands in the structure and append them at the end</p>
+                                </div>
+                                
+                                <div class="prep-option">
+                                    <div class="checkbox-with-button">
+                                        <label class="checkbox-container">
+                                            <input type="checkbox" id="separate-ligands">
+                                            <span class="checkmark"></span>
+                                            Create separate ligand file
+                                        </label>
+                                        <button class="btn btn-sm btn-outline-primary" id="download-ligand" disabled>
+                                            <i class="fas fa-download"></i>
+                                        </button>
+                                    </div>
+                                    <p class="option-description">Extract ligands to a separate PDB file for individual processing</p>
+                                </div>
+                                
+                                <div class="form-group">
+                                    <label>Select Ligands to Preserve</label>
+                                    <div id="ligand-selection" class="multi-checkbox-group">
+                                        <!-- Ligand checkboxes will be rendered here -->
+                                    </div>
+                                    <small class="form-help">Tick ligands to include. Unselected ligands will be ignored.</small>
+                                </div>
+                            </div>
+                        </div>
+
+                    </div>
+
+                    <div class="prep-actions">
+                        <button class="btn btn-primary" id="prepare-structure">
+                            <i class="fas fa-magic"></i> Prepare Structure
+                        </button>
+                        <button class="btn btn-secondary" id="preview-prepared">
+                            <i class="fas fa-eye"></i> Preview Prepared Structure
+                        </button>
+                        <button class="btn btn-info" id="download-prepared">
+                            <i class="fas fa-download"></i> Download Prepared PDB
+                        </button>
+                    </div>
+
+                    <div class="prep-status" id="prep-status" style="display: none;">
+                        <h3><i class="fas fa-info-circle"></i> Preparation Status</h3>
+                        <div class="status-content" id="prep-status-content">
+                            <!-- Status information will be displayed here -->
+                        </div>
+                    </div>
+
+                    <div class="prepared-structure-preview" id="prepared-structure-preview" style="display: none;">
+                        <h3><i class="fas fa-eye"></i> Prepared Structure Preview</h3>
+                        <div class="preview-content">
+                            <div class="structure-info">
+                                <p><strong>Original atoms</strong> <span style="font-size:0.9em; color:#6c757d;">(protein without H, before capping):</span> <span id="original-atoms"></span></p>
+                                <p><strong>Prepared atoms</strong> <span style="font-size:0.9em; color:#6c757d;">(protein without H, after capping):</span> <span id="prepared-atoms"></span></p>
+                                <p><strong>Removed components:</strong> <span id="removed-components"></span></p>
+                                <p><strong>Added capping groups:</strong> <span id="added-capping"></span></p>
+                                <p><strong>Ligands preserved:</strong> <span id="preserved-ligands"></span></p>
+                            </div>
+                            <div class="structure-visualization">
+                                <div id="prepared-molecule-viewer" class="molecule-viewer">
+                                    <div id="prepared-ngl-viewer" style="width: 100%; height: 100%; min-height: 300px;"></div>
+                                    <div id="prepared-viewer-controls" class="viewer-controls" style="display: none;">
+                                        <button class="btn btn-sm btn-secondary" onclick="mdPipeline.resetPreparedView()">
+                                            <i class="fas fa-home"></i> Reset View
+                                        </button>
+                                        <button class="btn btn-sm btn-secondary" onclick="mdPipeline.togglePreparedRepresentation()">
+                                            <i class="fas fa-eye"></i> <span id="prepared-style-text">Mixed View</span>
+                                        </button>
+                                        <button class="btn btn-sm btn-secondary" onclick="mdPipeline.togglePreparedSpin()">
+                                            <i class="fas fa-sync"></i> Spin
+                                        </button>
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+                    </div>
+
+                    <!-- Docking Section (visible only when ligands are preserved and present) -->
+                    <div class="card plumed-section-card" id="docking-section" style="display: none; margin-top: 20px;">
+                        <h2 class="plumed-toggle-header" id="docking-toggle-header">
+                            <i class="fas fa-vial"></i> Ligand Docking
+                            <i class="fas fa-chevron-down toggle-icon" id="docking-toggle-icon"></i>
+                        </h2>
+                        <p class="section-description">
+                            Configure docking for preserved ligands using AutoDock Vina and Meeko. Select which ligands to dock,
+                            define the Vina bounding box with live visualization, then run docking and choose poses.
+                        </p>
+                        <div class="custom-plumed-section" id="docking-content-section">
+                            <!-- Ligand Selection -->
+                            <div class="form-group" style="margin-bottom: 20px;">
+                                <label><i class="fas fa-pills"></i> Select Ligands to Dock</label>
+                                <p class="option-description" style="margin-bottom: 10px;">
+                                    Choose which preserved ligands should be included in docking calculations.
+                                </p>
+                                <div id="docking-ligand-selection" class="multi-checkbox-group">
+                                    <!-- Ligand checkboxes will be rendered here -->
+                                </div>
+                            </div>
+
+                            <!-- Collapsible: Docking Setup (Visualization + Box Dimensions) -->
+                            <div class="docking-setup-collapsible" style="margin-top: 10px; border: 1px solid #dee2e6; border-radius: 8px; overflow: hidden;">
+                                <div class="docking-setup-header" id="docking-setup-toggle" style="background: linear-gradient(135deg, #6f42c1 0%, #8e5dd4 100%); color: white; padding: 12px 15px; cursor: pointer; display: flex; justify-content: space-between; align-items: center;">
+                                    <span><i class="fas fa-cube"></i> Docking Search Space Setup</span>
+                                    <i class="fas fa-chevron-up" id="docking-setup-toggle-icon" style="transition: transform 0.3s ease;"></i>
+                                </div>
+                                <div class="docking-setup-content" id="docking-setup-content" style="padding: 15px; background: white;">
+                                    <!-- Docking Search Space Visualization -->
+                                    <div class="prepared-structure-preview" id="docking-structure-preview">
+                                        <h4 style="margin-top: 0;"><i class="fas fa-eye"></i> Search Space Visualization</h4>
+                                        <p class="card-description" style="margin-bottom: 10px;">
+                                            The protein–ligand system is shown below. For each selected ligand, a bounding box (10×10×10 Å by default)
+                                            represents the Vina search space. Adjust box dimensions below to update the visualization live.
+                                        </p>
+                                        <!-- NGL Viewer - Matching section 2 aspect ratio -->
+                                        <div id="docking-ngl-viewer" class="molecule-viewer" style="border: 2px solid #6f42c1; border-radius: 5px; width: 100%; max-width: 700px; height: 500px; position: relative; margin: 0 auto;">
+                                            <!-- Docking NGL visualization will be added here -->
+                                        </div>
+                                    </div>
+                                    
+                                    <!-- Box Dimensions - Below Visualization -->
+                                    <div id="docking-box-controls" style="margin-top: 15px; background: #f8f9fa; padding: 15px; border-radius: 5px; border: 1px solid #dee2e6;">
+                                        <h5 style="margin-top: 0; margin-bottom: 15px;"><i class="fas fa-sliders-h"></i> Box Dimensions for Selected Ligands</h5>
+                                        <div id="docking-setup-list" style="display: flex; flex-wrap: wrap; gap: 15px;">
+                                            <!-- Per-ligand box controls will be rendered here in a horizontal layout -->
+                                        </div>
+                                    </div>
+
+                                    <div class="prep-actions" style="margin-top: 15px;">
+                                        <button class="btn btn-primary" id="run-docking">
+                                            <i class="fas fa-vial"></i> Run Docking with Above Settings
+                                        </button>
+                                    </div>
+                                </div>
+                            </div>
+                            <div id="docking-status" class="status-message" style="display: none; margin-top: 10px;"></div>
+                            
+                            <div id="docking-poses-container" style="display: none; margin-top: 20px;">
+                                <h4><i class="fas fa-project-diagram"></i> Visualize Binding Poses</h4>
+                                <p class="option-description">
+                                    Browse through docked poses for each ligand. Use the navigation arrows to view different binding modes.
+                                    Select your preferred pose for the simulation.
+                                </p>
+                                
+                                <!-- Ligand selector tabs -->
+                                <div id="docking-ligand-tabs" class="docking-ligand-tabs">
+                                    <!-- Ligand tabs will be rendered here -->
+                                </div>
+                                
+                                <!-- 3D Viewer with pose navigation -->
+                                <div class="docking-poses-viewer-wrapper">
+                                    <div id="docking-poses-viewer" class="docking-poses-viewer"></div>
+                                    
+                                    <!-- Pose navigation controls overlay -->
+                                    <div class="pose-nav-controls">
+                                        <button type="button" class="pose-nav-btn pose-nav-prev" id="pose-prev-btn" title="Previous Pose">
+                                            <i class="fas fa-chevron-left"></i>
+                                        </button>
+                                        <div class="pose-info-display">
+                                            <div class="pose-mode-label" id="pose-mode-label">Original Ligand</div>
+                                            <div class="pose-energy-label" id="pose-energy-label"></div>
+                                            <div class="pose-color-legend">
+                                                <span><span class="legend-dot original"></span> Original (green)</span>
+                                                <span><span class="legend-dot docked"></span> Docked (coral)</span>
+                                            </div>
+                                        </div>
+                                        <button type="button" class="pose-nav-btn pose-nav-next" id="pose-next-btn" title="Next Pose">
+                                            <i class="fas fa-chevron-right"></i>
+                                        </button>
+                                    </div>
+                                </div>
+                                
+                                <!-- Pose selection summary -->
+                                <div id="docking-poses-list" class="docking-poses-selection">
+                                    <!-- Radio buttons for final selection will be rendered here -->
+                                </div>
+                                
+                                <div class="prep-actions" style="margin-top: 15px;">
+                                    <button class="btn btn-success" id="apply-docking-poses">
+                                        <i class="fas fa-check"></i> Use Selected Pose
+                                    </button>
+                                </div>
+                            </div>
+                        </div>
+                    </div>
+                </div>
+            </div>
+
+            <!-- Simulation Parameters Tab -->
+            <div id="simulation-params" class="tab-content">
+                <div class="card">
+                    <h2><i class="fas fa-sliders-h"></i> Simulation Parameters</h2>
+                    
+                    <div class="params-grid">
+                        <div class="param-section">
+                            <h3><i class="fas fa-cube"></i> System Setup</h3>
+                            <div class="form-group">
+                                <label for="box-type">Box Type:</label>
+                                <select id="box-type">
+                                    <option value="cuboid">Cuboid</option>
+                                </select>
+                            </div>
+                            <div class="form-group">
+                                <label for="box-size">
+                                    Distance (Å):
+                                    <i class="fas fa-info-circle" 
+                                       style="color: #007bff; margin-left: 5px; cursor: help;" 
+                                       data-toggle="tooltip" 
+                                       data-placement="top"
+                                       data-html="true"
+              title="The minimum distance between any atom originally present in solute and the edge of the periodic box is given by the distance parameter.">
+                                    </i>
+                                </label>
+                                <input type="number" id="box-size" value="10" step="1" min="5">
+                            </div>
+                        </div>
+
+                        <div class="param-section" id="ligand-forcefield-section" style="display: none;">
+                            <h3><i class="fas fa-atom"></i> Ligand Force Field</h3>
+                            <div class="form-group">
+                                <label for="ligand-forcefield">Ligand Force Field:</label>
+                                <select id="ligand-forcefield">
+                                    <option value="gaff2">gaff2</option>
+                                    <option value="gaff">gaff</option>
+                                </select>
+                            </div>
+                            <div class="form-group">
+                                <button type="button" class="btn btn-primary" onclick="mdPipeline.generateLigandFF(event)">
+                                    <i class="fas fa-cogs"></i> Generate FF for Ligand
+                                </button>
+                            </div>
+                        </div>
+
+                        <div class="param-section">
+                            <h3><i class="fas fa-flask"></i> Force Field & Water Model</h3>
+                            <div class="form-group">
+                                <label for="force-field">Protein Force Field:</label>
+                                <select id="force-field">
+                                    <option value="ff14SB">ff14SB</option>
+                                    <option value="ff19SB">ff19SB</option>
+                                </select>
+                            </div>
+                            <div class="form-group">
+                                <label for="water-model">Water Model:</label>
+                                <select id="water-model">
+                                    <option value="tip3p">TIP3P</option>
+                                    <option value="spce">SPCE</option>
+                                </select>
+                            </div>
+                            <div class="form-group">
+                                <label for="add-ions">Add Ions:</label>
+                                <div class="ion-controls">
+                                    <select id="add-ions">
+                                        <option value="None">None</option>
+                                        <option value="Na+">Na+</option>
+                                        <option value="Cl-">Cl-</option>
+                                    </select>
+                                    <button type="button" class="btn btn-sm btn-outline-primary" onclick="mdPipeline.calculateNetCharge(event)">
+                                        <i class="fas fa-calculator"></i> Net Charge
+                                    </button>
+                                </div>
+                            </div>
+                        </div>
+
+                        <div class="param-section">
+                            <h3><i class="fas fa-thermometer-half"></i> Temperature & Pressure</h3>
+                            <div class="form-group">
+                                <label for="temperature">Temperature (K):</label>
+                                <input type="number" id="temperature" value="300" step="5" min="200" max="400">
+                            </div>
+                            <div class="form-group">
+                                <label for="pressure">Pressure (atm):</label>
+                                <input type="number" id="pressure" value="1.0" step="0.1" min="0.1">
+                            </div>
+                            <div class="form-group">
+                                <label for="coupling-type">Thermostat:</label>
+                                <select id="coupling-type">
+                                    <option value="langevin">Langevin</option>
+                                </select>
+                            </div>
+                        </div>
+
+                        <div class="param-section">
+                            <h3><i class="fas fa-clock"></i> Integration Parameters</h3>
+                            <div class="form-group">
+                                <label for="timestep">Time Step (ps):</label>
+                                <input type="number" id="timestep" value="0.002" step="0.001" min="0.001" max="0.005">
+                            </div>
+                            <div class="form-group">
+                                <label for="cutoff">Cutoff Distance (Ang):</label>
+                                <input type="number" id="cutoff" value="10.0" step="1" min="8" max="20">
+                            </div>
+                            <div class="form-group">
+                                <label for="electrostatic">Electrostatic:</label>
+                                <select id="electrostatic">
+                                    <option value="pme">PME</option>
+                                </select>
+                            </div>
+                        </div>
+
+                    </div>
+                </div>
+            </div>
+
+            <!-- Simulation Steps Tab -->
+            <div id="simulation-steps" class="tab-content">
+                <div class="card">
+                    <h2><i class="fas fa-list-ol"></i> Simulation Steps Configuration</h2>
+                    
+                    <div class="steps-container">
+                        <div class="step-item">
+                            <div class="step-header">
+                                <h3><i class="fas fa-lock"></i> Restrained Minimization</h3>
+                                <label class="switch">
+                                    <input type="checkbox" id="enable-restrained-min" checked disabled>
+                                    <span class="slider"></span>
+                                </label>
+                            </div>
+                            <div class="step-content" id="restrained-min-content">
+                                <div class="form-row">
+                                    <div class="form-group">
+                                        <label for="restrained-steps">Steps:</label>
+                                        <input type="number" id="restrained-steps" value="10000" step="100" min="100">
+                                    </div>
+                                    <div class="form-group">
+                                        <label for="restrained-force">Force Constant (kJ/mol/Ų):</label>
+                                        <input type="number" id="restrained-force" value="10" step="1" min="1">
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+
+                        <div class="step-item">
+                            <div class="step-header">
+                                <h3><i class="fas fa-compress"></i> Minimization</h3>
+                                <label class="switch">
+                                    <input type="checkbox" id="enable-minimization" checked disabled>
+                                    <span class="slider"></span>
+                                </label>
+                            </div>
+                            <div class="step-content" id="minimization-content">
+                                <div class="form-row">
+                                    <div class="form-group">
+                                        <label for="min-steps">Steps:</label>
+                                        <input type="number" id="min-steps" value="20000" step="500" min="1000">
+                                    </div>
+                                    <div class="form-group">
+                                        <label for="min-algorithm">Algorithm:</label>
+                                        <select id="min-algorithm">
+                                            <option value="cg">Conjugate Gradient</option>
+                                        </select>
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+
+                        <div class="step-item">
+                            <div class="step-header">
+                                <h3><i class="fas fa-fire"></i> NPT Heating</h3>
+                                <label class="switch">
+                                    <input type="checkbox" id="enable-nvt" checked disabled>
+                                    <span class="slider"></span>
+                                </label>
+                            </div>
+                            <div class="step-content" id="nvt-content">
+                                <div class="form-row">
+                                    <div class="form-group">
+                                        <label for="nvt-steps">Steps:</label>
+                                        <input type="number" id="nvt-steps" value="50000" step="5000" min="10000">
+                                    </div>
+                                    <div class="form-group">
+                                        <label for="nvt-temp">Target Temperature (K):</label>
+                                        <input type="number" id="nvt-temp" value="300" step="5" min="200">
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+
+                        <div class="step-item">
+                            <div class="step-header">
+                                <h3><i class="fas fa-compress-arrows-alt"></i> NPT Equilibration</h3>
+                                <label class="switch">
+                                    <input type="checkbox" id="enable-npt" checked disabled>
+                                    <span class="slider"></span>
+                                </label>
+                            </div>
+                            <div class="step-content" id="npt-content">
+                                <div class="form-row">
+                                    <div class="form-group">
+                                        <label for="npt-steps">Steps:</label>
+                                        <input type="number" id="npt-steps" value="100000" step="10000" min="20000">
+                                    </div>
+                                    <div class="form-group">
+                                        <label for="npt-temp">Temperature (K):</label>
+                                        <input type="number" id="npt-temp" value="300" step="5" min="200">
+                                    </div>
+                                    <div class="form-group">
+                                        <label for="npt-pressure">Pressure (atm):</label>
+                                        <input type="number" id="npt-pressure" value="1.0" step="0.1" min="0.1">
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+
+                        <div class="step-item">
+                            <div class="step-header">
+                                <h3><i class="fas fa-play"></i> Production Run(NPT)</h3>
+                                <label class="switch">
+                                    <input type="checkbox" id="enable-production" checked disabled>
+                                    <span class="slider"></span>
+                                </label>
+                            </div>
+                            <div class="step-content" id="production-content">
+                                <div class="form-row">
+                                    <div class="form-group">
+                                        <label for="prod-steps">Steps:</label>
+                                        <input type="number" id="prod-steps" value="1000000" step="100000" min="100000">
+                                    </div>
+                                    <div class="form-group">
+                                        <label for="prod-temp">Temperature (K):</label>
+                                        <input type="number" id="prod-temp" value="300" step="5" min="200">
+                                    </div>
+                                    <div class="form-group">
+                                        <label for="prod-pressure">Pressure (atm):</label>
+                                        <input type="number" id="prod-pressure" value="1.0" step="0.1" min="0.1">
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+                    </div>
+                </div>
+            </div>
+
+            <!-- File Generation Tab -->
+            <div id="file-generation" class="tab-content">
+                <!-- Guidance Note Card -->
+                <div class="plumed-citation-note">
+                    <i class="fas fa-info-circle"></i>
+                    <div class="citation-content">
+                        <p>Click on <strong>Generate All Files</strong>. If you want to run <strong>biased simulations</strong> using PLUMED, proceed to the <strong>next section (PLUMED)</strong> to configure collective variables. Otherwise, download all files here and you're all set!</p>
+                    </div>
+                </div>
+                
+                <div class="card">
+                    <h2><i class="fas fa-file-download"></i> Generate Simulation Files</h2>
+                    
+                    <div class="generation-controls">
+                        <button class="btn btn-primary" id="generate-files">
+                            <i class="fas fa-magic"></i> Generate All Files
+                        </button>
+                        <button class="btn btn-secondary" id="preview-files">
+                            <i class="fas fa-eye"></i> Preview Files
+                        </button>
+                        <button class="btn btn-info" id="preview-solvated">
+                            <i class="fas fa-tint"></i> Preview Solvated Protein
+                        </button>
+                        <button class="btn btn-success" id="download-solvated">
+                            <i class="fas fa-download"></i> Download Solvated Protein
+                        </button>
+                    </div>
+
+                    <div class="files-preview" id="files-preview" style="display: none;">
+                        <div style="display: flex; justify-content: space-between; align-items: center; margin-bottom: 15px;">
+                            <h3 style="margin: 0;"><i class="fas fa-files"></i> Generated Files</h3>
+                            <button class="btn btn-primary" id="add-simulation-file" style="margin-left: 10px;">
+                                <i class="fas fa-plus"></i> Add Simulation File
+                            </button>
+                        </div>
+                        <div class="files-list" id="files-list">
+                            <!-- Generated files will be listed here -->
+                        </div>
+                    </div>
+
+                    <div class="download-section" id="download-section" style="display: none;">
+                        <h3><i class="fas fa-download"></i> Download Files</h3>
+                        <div class="download-options">
+                            <button class="btn btn-success" id="download-zip">
+                                <i class="fas fa-file-archive"></i> Download All as ZIP
+                            </button>
+                            
+                        </div>
+                    </div>
+
+                    <div class="simulation-summary" id="simulation-summary" style="display: none;">
+                        <h3><i class="fas fa-chart-line"></i> Simulation Summary</h3>
+                        <div class="summary-content" id="summary-content">
+                            <!-- Simulation summary will be displayed here -->
+                        </div>
+                    </div>
+                </div>
+            </div>
+            
+            <!-- PLUMED Section -->
+            <div id="plumed" class="tab-content">
+                <!-- PLUMED Citation Note -->
+                <div class="plumed-citation-note">
+                    <i class="fas fa-info-circle"></i>
+                    <div class="citation-content">
+                        <p><strong>Note:</strong> All CVs are taken from <a href="https://www.plumed.org/doc-v2.9/user-doc/html/index.html" target="_blank" rel="noopener noreferrer"><strong>PLUMED v2.9</strong> <i class="fas fa-external-link-alt"></i></a> documentation.</p>
+                        <p>If you use PLUMED in your research, please cite it. <a href="https://www.plumed.org/cite" target="_blank" rel="noopener noreferrer">Citation information <i class="fas fa-external-link-alt"></i></a></p>
+                    </div>
+                </div>
+                
+                <!-- PLUMED Collective Variables Section -->
+                <div class="card plumed-section-card">
+                    <h2>
+                        <i class="fas fa-chart-line"></i> PLUMED Collective Variables
+                    </h2>
+                    <p class="section-description">
+                        Configure Collective Variables (CVs) for biased MD simulations. Select a CV from the sidebar to view documentation and examples.
+                    </p>
+                    
+                    <div class="plumed-container" id="plumed-container">
+                        <!-- Left Sidebar: CV List -->
+                        <div class="plumed-sidebar">
+                            <div class="sidebar-header">
+                                <h3><i class="fas fa-list"></i> Collective Variables</h3>
+                                <div class="search-box">
+                                    <input type="text" id="cv-search" placeholder="Search CVs..." class="search-input">
+                                    <i class="fas fa-search search-icon"></i>
+                                </div>
+                            </div>
+                            <div class="cv-list" id="cv-list">
+                                <!-- CV items will be populated by JavaScript -->
+                            </div>
+                        </div>
+                        
+                        <!-- Right Panel: Documentation and Editor -->
+                        <div class="plumed-content">
+                            <div class="content-header" id="content-header" style="display: none;">
+                                <h3 id="cv-title"></h3>
+                            </div>
+                            
+                            <div class="content-body" id="content-body">
+                                <div class="welcome-message" id="welcome-message">
+                                    <i class="fas fa-hand-pointer fa-3x"></i>
+                                    <h3>Select a Collective Variable</h3>
+                                    <p>Choose a CV from the left sidebar to view its documentation and configure it for your simulation.</p>
+                                </div>
+                                
+                                <!-- Documentation Section -->
+                                <div class="cv-documentation" id="cv-documentation" style="display: none;">
+                                    <div class="doc-section" id="cv-module-section" style="display: none;">
+                                        <h4><i class="fas fa-puzzle-piece"></i> Module</h4>
+                                        <div class="doc-content" id="cv-module"></div>
+                                    </div>
+                                    
+                                    <div class="doc-section">
+                                        <h4><i class="fas fa-info-circle"></i> Description</h4>
+                                        <div class="doc-content" id="cv-description"></div>
+                                    </div>
+                                    
+                                    <div class="doc-section">
+                                        <h4><i class="fas fa-code"></i> Syntax</h4>
+                                        <div class="doc-content">
+                                            <pre class="syntax-box" id="cv-syntax"></pre>
+                                        </div>
+                                    </div>
+                                    
+                                    <div class="doc-section" id="cv-glossary-section" style="display: none;">
+                                        <h4><i class="fas fa-book"></i> Glossary of keywords and components</h4>
+                                        <div class="doc-content" id="cv-glossary"></div>
+                                    </div>
+                                    
+                                    <div class="doc-section" id="cv-options-section" style="display: none;">
+                                        <h4><i class="fas fa-list-ul"></i> Options</h4>
+                                        <div class="doc-content" id="cv-options"></div>
+                                    </div>
+                                    
+                                    <div class="doc-section" id="cv-components-section" style="display: none;">
+                                        <h4><i class="fas fa-cogs"></i> Components</h4>
+                                        <div class="doc-content" id="cv-components"></div>
+                                    </div>
+                                    
+                                    <div class="doc-section">
+                                        <h4><i class="fas fa-book"></i> Examples</h4>
+                                        <div class="doc-content">
+                                            <pre class="example-box" id="cv-example"></pre>
+                                        </div>
+                                    </div>
+                                    
+                                    <div class="doc-section" id="cv-notes-section" style="display: none;">
+                                        <h4><i class="fas fa-sticky-note"></i> Notes</h4>
+                                        <div class="doc-content" id="cv-notes"></div>
+                                    </div>
+                                    
+                                    <div class="doc-section" id="cv-related-section" style="display: none;">
+                                        <h4><i class="fas fa-link"></i> Related Collective Variables</h4>
+                                        <div class="doc-content" id="cv-related"></div>
+                                    </div>
+                                </div>
+                                
+                                <!-- Editable Editor Section -->
+                                <div class="cv-editor-section" id="cv-editor-section" style="display: none;">
+                                    <div class="editor-header">
+                                        <h4><i class="fas fa-edit"></i> Your Configuration</h4>
+                                        <div class="editor-actions">
+                                            <button class="btn btn-sm btn-info" id="copy-config">
+                                                <i class="fas fa-copy"></i> Copy
+                                            </button>
+                                            <button class="btn btn-sm btn-primary" id="view-pdb">
+                                                <i class="fas fa-eye"></i> View PDB
+                                            </button>
+                                            <button class="btn btn-sm btn-secondary" id="reset-cv">
+                                                <i class="fas fa-redo"></i> Reset to Example
+                                            </button>
+                                            <button class="btn btn-sm btn-success" id="save-config">
+                                                <i class="fas fa-save"></i> Save
+                                            </button>
+                                        </div>
+                                    </div>
+                                    <textarea id="cv-editor" class="cv-editor" placeholder="Enter your PLUMED configuration here..."></textarea>
+                                    <div class="editor-footer">
+                                        <span class="char-count"><span id="char-count">0</span> characters</span>
+                                        <span class="line-count"><span id="line-count">0</span> lines</span>
+                                    </div>
+                                </div>
+                                
+                                <!-- Saved Configurations -->
+                                <div class="saved-configs" id="saved-configs" style="display: none;">
+                                    <h4><i class="fas fa-bookmark"></i> Saved Configurations</h4>
+                                    <div class="configs-list" id="configs-list">
+                                        <!-- Saved configs will be shown here -->
+                                    </div>
+                                </div>
+                            </div>
+                        </div>
+                    </div>
+                </div>
+                
+                <!-- Custom PLUMED File Section -->
+                <div class="card plumed-section-card" id="custom-plumed-card">
+                    <h2 class="plumed-toggle-header" id="custom-plumed-toggle-header">
+                        <i class="fas fa-file-code"></i> Write Custom PLUMED File
+                        <i class="fas fa-chevron-down toggle-icon" id="custom-plumed-toggle-icon"></i>
+                    </h2>
+                    <p class="section-description">
+                        Write your custom PLUMED configuration from scratch. This editor allows you to create a complete PLUMED input file.
+                    </p>
+                    
+                    <div class="custom-plumed-section" id="custom-plumed-section">
+                        <div class="custom-editor-header">
+                            <h4><i class="fas fa-edit"></i> Custom PLUMED Configuration</h4>
+                            <div class="editor-actions">
+                                <button class="btn btn-sm btn-info" id="copy-custom-plumed">
+                                    <i class="fas fa-copy"></i> Copy
+                                </button>
+                                <button class="btn btn-sm btn-primary" id="view-pdb-custom">
+                                    <i class="fas fa-eye"></i> View PDB
+                                </button>
+                                <button class="btn btn-sm btn-success" id="download-custom-plumed">
+                                    <i class="fas fa-save"></i> Save
+                                </button>
+                                <button class="btn btn-sm btn-secondary" id="clear-custom-plumed">
+                                    <i class="fas fa-trash"></i> Clear
+                                </button>
+                            </div>
+                        </div>
+                        <textarea id="custom-plumed-editor" class="custom-plumed-editor" placeholder="Write your PLUMED configuration here...&#10;&#10;Example:&#10;# PLUMED input file&#10;d1: DISTANCE ATOMS=1,2&#10;PRINT ARG=d1 FILE=colvar.dat"></textarea>
+                        <div class="editor-footer">
+                            <span class="char-count"><span id="custom-char-count">0</span> characters</span>
+                            <span class="line-count"><span id="custom-line-count">0</span> lines</span>
+                        </div>
+                    </div>
+                </div>
+                
+                <!-- Generate Simulation Files Section -->
+                <div class="card plumed-section-card" id="generate-simulation-files-card">
+                    <h2 class="plumed-toggle-header" id="generate-simulation-files-toggle-header">
+                        <i class="fas fa-cogs"></i> Generate Simulation Files
+                        <i class="fas fa-chevron-down toggle-icon" id="generate-simulation-files-toggle-icon"></i>
+                    </h2>
+                    <p class="section-description">
+                        Generate and download simulation files for your PLUMED setup.
+                    </p>
+                    
+                    <div class="generate-simulation-files-section" id="generate-simulation-files-section">
+                        <div class="generation-controls" style="display: flex; gap: 10px; padding: 20px;">
+                            <button class="btn btn-primary" id="plumed-generate-files">
+                                <i class="fas fa-magic"></i> Generate Files
+                            </button>
+                            <button class="btn btn-secondary" id="plumed-preview-files">
+                                <i class="fas fa-eye"></i> Preview Files
+                            </button>
+                            <button class="btn btn-success" id="plumed-download-files">
+                                <i class="fas fa-download"></i> Download Files
+                            </button>
+                        </div>
+                    </div>
+                </div>
+            </div>
+        </main>
+        
+        <!-- Step Navigation Controls -->
+        <div class="step-navigation">
+            <button class="nav-btn prev-btn" id="prev-tab" disabled>
+                <i class="fas fa-chevron-left"></i> Previous
+            </button>
+            <div class="step-indicator">
+                <span id="current-step">1</span> of <span id="total-steps">7</span>
+            </div>
+            <button class="nav-btn next-btn" id="next-tab">
+                Next <i class="fas fa-chevron-right"></i>
+            </button>
+        </div>
+
+        <!-- Footer -->
+        <footer class="footer">
+            <p>&copy; 2025 MD Simulation Pipeline. Built for molecular dynamics simulations.</p>
+        </footer>
+    </div>
+
+        <!-- PDB Viewer Modal -->
+        <div class="modal" id="pdb-viewer-modal" style="display: none; position: fixed; top: 0; left: 0; width: 100%; height: 100%; background: rgba(0,0,0,0.5); z-index: 10000; overflow: auto;">
+            <div class="modal-content" style="max-width: 90%; max-height: 90vh; margin: 5vh auto; background: white; border-radius: 8px; box-shadow: 0 4px 6px rgba(0,0,0,0.1);">
+                <div class="modal-header" style="display: flex; justify-content: space-between; align-items: center; padding: 15px; border-bottom: 1px solid #ddd; background: #f8f9fa; border-radius: 8px 8px 0 0;">
+                    <h3 style="margin: 0;"><i class="fas fa-file-code"></i> Viewer PDB File</h3>
+                    <button class="btn btn-sm btn-secondary" id="close-pdb-modal" style="margin: 0;">
+                        <i class="fas fa-times"></i> Close
+                    </button>
+                </div>
+                <div class="modal-body" style="padding: 15px; overflow: auto; max-height: calc(90vh - 100px);">
+                    <div id="pdb-content-loading" style="text-align: center; padding: 20px;">
+                        <i class="fas fa-spinner fa-spin"></i> Loading PDB file...
+                    </div>
+                    <div id="pdb-content-error" style="display: none; color: #dc3545; padding: 20px; text-align: center;">
+                        <i class="fas fa-exclamation-triangle"></i> <span id="pdb-error-message"></span>
+                    </div>
+                    <pre id="pdb-content" style="display: none; font-family: 'Courier New', monospace; font-size: 12px; line-height: 1.4; background: #f8f9fa; padding: 15px; border-radius: 4px; overflow-x: auto; white-space: pre-wrap; word-wrap: break-word;"></pre>
+                </div>
+            </div>
+    </div>
+
+    <script src="../js/script.js"></script>
+    <script src="../js/plumed_cv_docs.js"></script>
+    <script src="../js/plumed.js"></script>
+</body>
+</html>

ambermdflow/html/plumed.html

@@ -0,0 +1,99 @@
+<!-- PLUMED Collective Variables Section -->
+<div id="plumed" class="tab-content">
+    <div class="card">
+        <h2><i class="fas fa-chart-line"></i> PLUMED Collective Variables</h2>
+        <p class="section-description">
+            Configure Collective Variables (CVs) for biased MD simulations. Select a CV from the sidebar to view documentation and examples.
+        </p>
+        
+        <div class="plumed-container">
+            <!-- Left Sidebar: CV List -->
+            <div class="plumed-sidebar">
+                <div class="sidebar-header">
+                    <h3><i class="fas fa-list"></i> Collective Variables</h3>
+                    <div class="search-box">
+                        <input type="text" id="cv-search" placeholder="Search CVs..." class="search-input">
+                        <i class="fas fa-search search-icon"></i>
+                    </div>
+                </div>
+                <div class="cv-list" id="cv-list">
+                    <!-- CV items will be populated by JavaScript -->
+                </div>
+            </div>
+            
+            <!-- Right Panel: Documentation and Editor -->
+            <div class="plumed-content">
+                <div class="content-header" id="content-header" style="display: none;">
+                    <h3 id="cv-title"></h3>
+                    <button class="btn btn-sm btn-secondary" id="reset-cv">
+                        <i class="fas fa-redo"></i> Reset to Example
+                    </button>
+                </div>
+                
+                <div class="content-body" id="content-body">
+                    <div class="welcome-message" id="welcome-message">
+                        <i class="fas fa-hand-pointer fa-3x"></i>
+                        <h3>Select a Collective Variable</h3>
+                        <p>Choose a CV from the left sidebar to view its documentation and configure it for your simulation.</p>
+                    </div>
+                    
+                    <!-- Documentation Section -->
+                    <div class="cv-documentation" id="cv-documentation" style="display: none;">
+                        <div class="doc-section">
+                            <h4><i class="fas fa-info-circle"></i> Description</h4>
+                            <div class="doc-content" id="cv-description"></div>
+                        </div>
+                        
+                        <div class="doc-section">
+                            <h4><i class="fas fa-code"></i> Syntax</h4>
+                            <div class="doc-content">
+                                <pre class="syntax-box" id="cv-syntax"></pre>
+                            </div>
+                        </div>
+                        
+                        <div class="doc-section">
+                            <h4><i class="fas fa-book"></i> Example</h4>
+                            <div class="doc-content">
+                                <pre class="example-box" id="cv-example"></pre>
+                            </div>
+                        </div>
+                        
+                        <div class="doc-section" id="cv-components-section" style="display: none;">
+                            <h4><i class="fas fa-cogs"></i> Components</h4>
+                            <div class="doc-content" id="cv-components"></div>
+                        </div>
+                    </div>
+                    
+                    <!-- Editable Editor Section -->
+                    <div class="cv-editor-section" id="cv-editor-section" style="display: none;">
+                        <div class="editor-header">
+                            <h4><i class="fas fa-edit"></i> Your Configuration</h4>
+                            <div class="editor-actions">
+                                <button class="btn btn-sm btn-info" id="copy-config">
+                                    <i class="fas fa-copy"></i> Copy
+                                </button>
+                                <button class="btn btn-sm btn-success" id="save-config">
+                                    <i class="fas fa-save"></i> Save
+                                </button>
+                            </div>
+                        </div>
+                        <textarea id="cv-editor" class="cv-editor" placeholder="Enter your PLUMED configuration here..."></textarea>
+                        <div class="editor-footer">
+                            <span class="char-count"><span id="char-count">0</span> characters</span>
+                            <span class="line-count"><span id="line-count">0</span> lines</span>
+                        </div>
+                    </div>
+                    
+                    <!-- Saved Configurations -->
+                    <div class="saved-configs" id="saved-configs" style="display: none;">
+                        <h4><i class="fas fa-bookmark"></i> Saved Configurations</h4>
+                        <div class="configs-list" id="configs-list">
+                            <!-- Saved configs will be shown here -->
+                        </div>
+                    </div>
+                </div>
+            </div>
+        </div>
+    </div>
+</div>
+

ambermdflow/structure_preparation.py

@@ -0,0 +1,1194 @@
+#!/usr/bin/env python3
+"""
+AMBER Structure Preparation Script using MDAnalysis
+Complete pipeline: extract protein, add caps, handle ligands
+"""
+
+import glob
+import os
+import re
+import subprocess
+import sys
+import shutil
+import logging
+from pathlib import Path
+
+logger = logging.getLogger(__name__)
+
+def run_command(cmd, description=""):
+    """Run a command and return success status"""
+    try:
+        print(f"Running: {description}")
+        print(f"Command: {cmd}")
+        result = subprocess.run(cmd, shell=True, capture_output=True, text=True, timeout=120)
+        print(f"Return code: {result.returncode}")
+        if result.stdout:
+            print(f"STDOUT: {result.stdout}")
+        if result.stderr:
+            print(f"STDERR: {result.stderr}")
+        if result.returncode != 0:
+            print(f"Error: {result.stderr}")
+            return False
+        return True
+    except subprocess.TimeoutExpired:
+        print(f"Timeout: {description}")
+        return False
+    except Exception as e:
+        print(f"Error running {description}: {str(e)}")
+        return False
+
+def extract_protein_only(pdb_content, output_file, selected_chains=None):
+    """Extract protein without hydrogens using MDAnalysis. Optionally restrict to selected chains."""
+    # Write input content to output file first
+    with open(output_file, 'w') as f:
+        f.write(pdb_content)
+    
+    try:
+        # Run MDAnalysis command with the output file as input
+        chain_sel = ''
+        if selected_chains:
+            chain_filters = ' or '.join([f'chain {c}' for c in selected_chains])
+            chain_sel = f' and ({chain_filters})'
+        selection = f"protein{chain_sel} and not name H* 1H* 2H* 3H*"
+        abspath = os.path.abspath(output_file)
+        cmd = f'python -c "import MDAnalysis as mda; u=mda.Universe(\'{abspath}\'); u.select_atoms(\'{selection}\').write(\'{abspath}\')"'
+        result = subprocess.run(cmd, shell=True, capture_output=True, text=True, timeout=60)
+        
+        if result.returncode != 0:
+            raise Exception(f"MDAnalysis error: {result.stderr}")
+        
+        return True
+    except Exception as e:
+        print(f"Error in extract_protein_only: {e}")
+        return False
+
+def add_capping_groups(input_file, output_file):
+    """Add ACE and NME capping groups using add_caps.py"""
+    add_caps_script = (Path(__file__).resolve().parent / "add_caps.py")
+    # First add caps
+    temp_capped = output_file.replace('.pdb', '_temp.pdb')
+    cmd = f"python {add_caps_script} -i {input_file} -o {temp_capped}"
+    if not run_command(cmd, f"Adding capping groups to {input_file}"):
+        return False
+    
+    # Then add TER cards using awk
+    cmd = f"awk '/NME/{{nme=NR}} /ACE/ && nme && NR > nme {{print \"TER\"; nme=0}} {{print}}' {temp_capped} > {output_file}"
+    if not run_command(cmd, f"Adding TER cards to {temp_capped}"):
+        return False
+    
+    # Clean up temp file
+    if os.path.exists(temp_capped):
+        os.remove(temp_capped)
+    
+    return True
+
+
+def replace_chain_in_pdb(target_pdb, chain_id, source_pdb):
+    """
+    Replace a specific chain in target_pdb with the chain from source_pdb.
+    Only performs replacement if the target actually contains the chain_id.
+    Used to merge ESMFold-minimized chains into 1_protein_no_hydrogens.pdb.
+    If the source has no ATOM lines (or none matching the chain), we do NOT
+    modify the target, to avoid wiping the protein when the minimized file is
+    empty or has an unexpected format.
+    """
+    with open(target_pdb, 'r') as f:
+        target_lines = f.readlines()
+    if not any(
+        ln.startswith(('ATOM', 'HETATM')) and len(ln) >= 22 and ln[21] == chain_id
+        for ln in target_lines
+    ):
+        return
+    with open(source_pdb, 'r') as f:
+        source_lines = f.readlines()
+    source_chain_lines = []
+    for ln in source_lines:
+        if ln.startswith(('ATOM', 'HETATM')) and len(ln) >= 22:
+            ch = ln[21]
+            if ch == 'A' or ch == chain_id:
+                source_chain_lines.append(ln[:21] + chain_id + ln[22:])
+    if not source_chain_lines:
+        # Fallback: minimized PDB may use chain ' ' or other; take all ATOM/HETATM.
+        for ln in source_lines:
+            if ln.startswith(('ATOM', 'HETATM')) and len(ln) >= 22:
+                source_chain_lines.append(ln[:21] + chain_id + ln[22:])
+    if not source_chain_lines:
+        return  # Do not modify target: we have nothing to add; avoid wiping the protein.
+    filtered_target = [
+        ln for ln in target_lines
+        if not (ln.startswith(('ATOM', 'HETATM')) and len(ln) >= 22 and ln[21] == chain_id)
+    ]
+    combined = []
+    for ln in filtered_target:
+        if ln.startswith('END'):
+            combined.extend(source_chain_lines)
+            combined.append("TER\n")
+        combined.append(ln)
+    with open(target_pdb, 'w') as f:
+        f.writelines(combined)
+
+
+def extract_selected_chains(pdb_content, output_file, selected_chains):
+    """Extract selected chains using PyMOL commands"""
+    try:
+        # Write input content to temp file
+        temp_input = output_file.replace('.pdb', '_temp_input.pdb')
+        with open(temp_input, 'w') as f:
+            f.write(pdb_content)
+        
+        # Build chain selection string
+        chain_filters = ' or '.join([f'chain {c}' for c in selected_chains])
+        selection = f"({chain_filters}) and polymer.protein"
+        
+        # Use PyMOL to extract chains
+        cmd = f'''python -c "
+import pymol
+pymol.finish_launching(['pymol', '-c'])
+pymol.cmd.load('{temp_input}')
+pymol.cmd.save('{output_file}', '{selection}')
+pymol.cmd.quit()
+"'''
+        
+        result = subprocess.run(cmd, shell=True, capture_output=True, text=True, timeout=60)
+        
+        # Clean up temp file
+        if os.path.exists(temp_input):
+            os.remove(temp_input)
+        
+        if result.returncode != 0:
+            print(f"PyMOL chain extraction error: {result.stderr}")
+            return False
+        
+        return True
+    except Exception as e:
+        print(f"Error extracting selected chains: {e}")
+        return False
+
+def extract_selected_ligands(pdb_content, output_file, selected_ligands):
+    """Extract selected ligands using PyMOL commands.
+    selected_ligands: list of dicts with resn, chain, and optionally resi.
+    When resi is provided, use (resn X and chain Y and resi Z) to uniquely pick
+    one instance when the same ligand (resn) appears multiple times in the same chain.
+    """
+    try:
+        # Write input content to temp file
+        temp_input = output_file.replace('.pdb', '_temp_input.pdb')
+        with open(temp_input, 'w') as f:
+            f.write(pdb_content)
+        
+        # Build ligand selection string (include resi when present to disambiguate duplicates)
+        parts = []
+        for lig in selected_ligands:
+            resn = lig.get('resn', '').strip()
+            chain = lig.get('chain', '').strip()
+            resi = lig.get('resi') if lig.get('resi') is not None else ''
+            resi = str(resi).strip() if resi else ''
+            if resn and chain:
+                if resi:
+                    parts.append(f"(resn {resn} and chain {chain} and resi {resi})")
+                else:
+                    parts.append(f"(resn {resn} and chain {chain})")
+            elif resn:
+                parts.append(f"resn {resn}")
+        
+        if not parts:
+            # No ligands to extract
+            with open(output_file, 'w') as f:
+                f.write('\n')
+            return True
+        
+        selection = ' or '.join(parts)
+        
+        # Use PyMOL to extract ligands
+        cmd = f'''python -c "
+import pymol
+pymol.finish_launching(['pymol', '-c'])
+pymol.cmd.load('{temp_input}')
+pymol.cmd.save('{output_file}', '{selection}')
+pymol.cmd.quit()
+"'''
+        
+        result = subprocess.run(cmd, shell=True, capture_output=True, text=True, timeout=60)
+        
+        # Clean up temp file
+        if os.path.exists(temp_input):
+            os.remove(temp_input)
+        
+        if result.returncode != 0:
+            print(f"PyMOL ligand extraction error: {result.stderr}")
+            return False
+        
+        return True
+    except Exception as e:
+        print(f"Error extracting selected ligands: {e}")
+        return False
+
+def extract_ligands(pdb_content, output_file, ligand_residue_name=None, selected_ligands=None):
+    """Extract ligands using MDAnalysis. Optionally restrict to selected ligands (list of dicts with resn, chain, resi)."""
+    # Write input content to output file first
+    with open(output_file, 'w') as f:
+        f.write(pdb_content)
+    
+    try:
+        # Run MDAnalysis command with the output file as input
+        if selected_ligands:
+            # Build selection from provided ligand list; include resid when present to disambiguate
+            # when the same ligand (resn) appears multiple times in the same chain (GOL-A-1, GOL-A-2)
+            parts = []
+            for lig in selected_ligands:
+                resn = lig.get('resn', '').strip()
+                chain = lig.get('chain', '').strip()
+                resi = lig.get('resi') if lig.get('resi') is not None else ''
+                resi = str(resi).strip() if resi else ''
+                if resn and chain:
+                    if resi:
+                        # Extract leading digits for resid in case of insertion codes (e.g. 100A -> 100)
+                        m = re.search(r'^(-?\d+)', resi)
+                        resid_val = m.group(1) if m else resi
+                        parts.append(f"(resname {resn} and segid {chain} and resid {resid_val})")
+                    else:
+                        parts.append(f"(resname {resn} and segid {chain})")
+                elif resn:
+                    parts.append(f"resname {resn}")
+            if parts:
+                selection = ' or '.join(parts)
+                cmd = f'''python -c "
+import MDAnalysis as mda
+u = mda.Universe('{output_file}')
+u.select_atoms('{selection}').write('{output_file}')
+"'''
+            else:
+                cmd = f"python -c \"open('{output_file}','w').write('\\n')\""
+        elif ligand_residue_name:
+            # Use specified ligand residue name - extract from both ATOM and HETATM records
+            cmd = f'''python -c "
+import MDAnalysis as mda
+u = mda.Universe('{output_file}')
+# Extract specific ligand residue from both ATOM and HETATM records
+u.select_atoms('resname {ligand_residue_name}').write('{output_file}')
+"'''
+        else:
+            # Auto-detect ligand residues
+            cmd = f'''python -c "
+import MDAnalysis as mda
+u = mda.Universe('{output_file}')
+# Get all unique residue names from HETATM records
+hetatm_residues = set()
+for atom in u.atoms:
+    if atom.record_type == 'HETATM':
+        hetatm_residues.add(atom.resname)
+# Remove water and ions
+ligand_residues = hetatm_residues - {{'HOH', 'WAT', 'TIP3', 'TIP4', 'SPC', 'SPCE', 'NA', 'CL', 'K', 'MG', 'CA', 'ZN', 'FE', 'MN', 'CU', 'NI', 'CO', 'CD', 'HG', 'PB', 'SR', 'BA', 'RB', 'CS', 'LI', 'F', 'BR', 'I', 'PO4', 'PO3', 'H2PO4', 'HPO4', 'H3PO4', 'SO4'}}
+if ligand_residues:
+    resname_sel = ' or '.join([f'resname {{res}}' for res in ligand_residues])
+    u.select_atoms(resname_sel).write('{output_file}')
+else:
+    # No ligands found, create empty file
+    with open('{output_file}', 'w') as f:
+        f.write('\\n')
+"'''
+        result = subprocess.run(cmd, shell=True, capture_output=True, text=True, timeout=60)
+        
+        if result.returncode != 0:
+            raise Exception(f"MDAnalysis error: {result.stderr}")
+        
+        # If specific ligand residue name was provided, convert ATOM to HETATM
+        if ligand_residue_name:
+            convert_atom_to_hetatm(output_file)
+        
+        return True
+    except Exception as e:
+        print(f"Error in extract_ligands: {e}")
+        return False
+
+def convert_atom_to_hetatm(pdb_file):
+    """Convert ATOM records to HETATM in PDB file"""
+    try:
+        with open(pdb_file, 'r') as f:
+            lines = f.readlines()
+        
+        # Convert ATOM to HETATM
+        converted_lines = []
+        for line in lines:
+            if line.startswith('ATOM'):
+                # Replace ATOM with HETATM
+                converted_line = 'HETATM' + line[6:]
+                converted_lines.append(converted_line)
+            else:
+                converted_lines.append(line)
+        
+        # Write back to file
+        with open(pdb_file, 'w') as f:
+            f.writelines(converted_lines)
+        
+        print(f"Converted ATOM records to HETATM in {pdb_file}")
+        return True
+    except Exception as e:
+        print(f"Error converting ATOM to HETATM: {e}")
+        return False
+
+def extract_original_residue_info(ligand_file):
+    """Extract original residue name, chain ID, and residue number from ligand PDB file"""
+    residue_info = {}
+    try:
+        with open(ligand_file, 'r') as f:
+            for line in f:
+                if line.startswith(('ATOM', 'HETATM')):
+                    resname = line[17:20].strip()
+                    chain_id = line[21:22].strip()
+                    resnum = line[22:26].strip()
+                    # Store the first residue info we find (assuming single residue per file)
+                    if resname and resname not in residue_info:
+                        residue_info = {
+                            'resname': resname,
+                            'chain_id': chain_id,
+                            'resnum': resnum
+                        }
+                        break  # We only need the first residue info
+        return residue_info
+    except Exception as e:
+        print(f"Error extracting residue info: {e}")
+        return {}
+
+def restore_residue_info_in_pdb(pdb_file, original_resname, original_chain_id, original_resnum):
+    """Restore original residue name, chain ID, and residue number in PDB file"""
+    try:
+        with open(pdb_file, 'r') as f:
+            lines = f.readlines()
+        
+        restored_lines = []
+        for line in lines:
+            if line.startswith(('ATOM', 'HETATM')):
+                # Restore residue name (columns 17-20)
+                restored_line = line[:17] + f"{original_resname:>3}" + line[20:]
+                # Restore chain ID (column 21)
+                if original_chain_id:
+                    restored_line = restored_line[:21] + original_chain_id + restored_line[22:]
+                # Restore residue number (columns 22-26)
+                if original_resnum:
+                    restored_line = restored_line[:22] + f"{original_resnum:>4}" + restored_line[26:]
+                restored_lines.append(restored_line)
+            elif line.startswith('MASTER'):
+                # Skip MASTER records
+                continue
+            else:
+                restored_lines.append(line)
+        
+        with open(pdb_file, 'w') as f:
+            f.writelines(restored_lines)
+        
+        print(f"Restored residue info: {original_resname} {original_chain_id} {original_resnum} in {pdb_file}")
+        return True
+    except Exception as e:
+        print(f"Error restoring residue info: {e}")
+        return False
+
+def correct_ligand_with_openbabel(ligand_file, corrected_file):
+    """Correct ligand using OpenBabel (add hydrogens at pH 7.4) and preserve original residue info"""
+    ligand_path = os.path.abspath(ligand_file)
+    corrected_path = os.path.abspath(corrected_file)
+    if not os.path.isfile(ligand_path) or os.path.getsize(ligand_path) == 0:
+        print("Ligand file missing or empty:", ligand_path)
+        return False
+
+    # Extract original residue info before OpenBabel processing
+    residue_info = extract_original_residue_info(ligand_path)
+    original_resname = residue_info.get('resname', 'UNL')
+    original_chain_id = residue_info.get('chain_id', '')
+    original_resnum = residue_info.get('resnum', '1')
+    
+    print(f"Original residue info: {original_resname} {original_chain_id} {original_resnum}")
+
+    # Use OpenBabel to add hydrogens at pH 7.4
+    cmd = f'obabel -i pdb {ligand_path} -o pdb -O {corrected_path} -p 7.4'
+    success = run_command(cmd, f"Correcting ligand with OpenBabel")
+    
+    if not success:
+        return False
+    
+    # Restore original residue name, chain ID, and residue number
+    if residue_info:
+        restore_residue_info_in_pdb(corrected_path, original_resname, original_chain_id, original_resnum)
+    
+    return True
+
+def split_ligands_by_residue(ligand_file, output_dir):
+    """Split multi-ligand PDB file into individual ligand files using MDAnalysis (one file per residue)
+    This is more robust than splitting by TER records as it properly handles residue-based splitting.
+    """
+    ligand_files = []
+    try:
+        ligand_path = os.path.abspath(ligand_file)
+        output_dir_abs = os.path.abspath(output_dir)
+        
+        # Use MDAnalysis to split ligands by residue - this is the robust method
+        # Command: python -c "import MDAnalysis as mda; u=mda.Universe('3_ligands_extracted.pdb'); [res.atoms.write(f'3_ligand_extracted_{i}.pdb') for i,res in enumerate(u.residues,1)]"
+        cmd = f'''python -c "import MDAnalysis as mda; import os; u=mda.Universe('{ligand_path}'); os.chdir('{output_dir_abs}'); [res.atoms.write(f'3_ligand_extracted_{{i}}.pdb') for i,res in enumerate(u.residues,1)]"'''
+        
+        print(f"Running MDAnalysis command to split ligands by residue...")
+        result = subprocess.run(cmd, shell=True, capture_output=True, text=True, cwd=output_dir_abs)
+        
+        if result.returncode != 0:
+            print(f"Error running MDAnalysis command: {result.stderr}")
+            print(f"Command output: {result.stdout}")
+            return []
+        
+        # Collect all generated ligand files
+        ligand_files = []
+        for f in os.listdir(output_dir):
+            if f.startswith('3_ligand_extracted_') and f.endswith('.pdb'):
+                ligand_files.append(os.path.join(output_dir, f))
+        
+        # Sort by number in filename (e.g., 3_ligand_extracted_1.pdb, 3_ligand_extracted_2.pdb, ...)
+        ligand_files.sort(key=lambda x: int(os.path.basename(x).split('_')[-1].split('.')[0]))
+        
+        print(f"Split {len(ligand_files)} ligand(s) from {ligand_file}")
+        return ligand_files
+    except Exception as e:
+        print(f"Error splitting ligands: {e}")
+        import traceback
+        traceback.print_exc()
+        return []
+
+def remove_connect_records(pdb_file):
+    """Remove CONNECT and MASTER records from PDB file"""
+    try:
+        with open(pdb_file, 'r') as f:
+            lines = f.readlines()
+        
+        # Filter out CONNECT and MASTER records
+        filtered_lines = [line for line in lines if not line.startswith(('CONECT', 'MASTER'))]
+        
+        with open(pdb_file, 'w') as f:
+            f.writelines(filtered_lines)
+        
+        print(f"Removed CONNECT and MASTER records from {pdb_file}")
+        return True
+    except Exception as e:
+        print(f"Error removing CONNECT/MASTER records: {e}")
+        return False
+
+def convert_atom_to_hetatm_in_ligand(pdb_file):
+    """Convert ATOM records to HETATM in ligand PDB file for consistency"""
+    try:
+        with open(pdb_file, 'r') as f:
+            lines = f.readlines()
+        
+        converted_lines = []
+        converted_count = 0
+        for line in lines:
+            if line.startswith('ATOM'):
+                # Replace ATOM with HETATM, preserving the rest of the line
+                converted_line = 'HETATM' + line[6:]
+                converted_lines.append(converted_line)
+                converted_count += 1
+            else:
+                converted_lines.append(line)
+        
+        with open(pdb_file, 'w') as f:
+            f.writelines(converted_lines)
+        
+        if converted_count > 0:
+            print(f"Converted {converted_count} ATOM record(s) to HETATM in {pdb_file}")
+        
+        return True
+    except Exception as e:
+        print(f"Error converting ATOM to HETATM: {e}")
+        return False
+
+def make_atom_names_distinct(pdb_file):
+    """Make all atom names distinct (C1, C2, O1, O2, H1, H2, etc.) for antechamber compatibility
+    Antechamber requires each atom to have a unique name.
+    """
+    try:
+        from collections import defaultdict
+        
+        with open(pdb_file, 'r') as f:
+            lines = f.readlines()
+        
+        # Track counts for each element type
+        element_counts = defaultdict(int)
+        modified_lines = []
+        modified_count = 0
+        
+        for line in lines:
+            if line.startswith(('ATOM', 'HETATM')):
+                # Extract element from the last field (column 76-78) or from atom name (columns 12-16)
+                # Try to get element from the last field first (more reliable)
+                element = line[76:78].strip()
+                
+                # If element not found in last field, try to extract from atom name
+                if not element:
+                    atom_name = line[12:16].strip()
+                    # Extract element symbol (first letter, or first two letters for two-letter elements)
+                    if len(atom_name) >= 1:
+                        # Check for two-letter elements (common ones: Cl, Br, etc.)
+                        if len(atom_name) >= 2 and atom_name[:2].upper() in ['CL', 'BR', 'MG', 'CA', 'ZN', 'FE', 'MN', 'CU', 'NI', 'CO', 'CD', 'HG', 'PB', 'SR', 'BA', 'RB', 'CS', 'LI']:
+                            element = atom_name[:2].upper()
+                        else:
+                            element = atom_name[0].upper()
+                
+                # Increment count for this element
+                element_counts[element] += 1
+                count = element_counts[element]
+                
+                # Create distinct atom name: Element + number (e.g., C1, C2, O1, O2, H1, H2)
+                # Atom name is in columns 12-16 (4 characters, right-aligned)
+                distinct_name = f"{element}{count}"
+                
+                # Ensure the name fits in 4 characters (right-aligned)
+                if len(distinct_name) > 4:
+                    # For long element names, use abbreviation or truncate
+                    if element == 'CL':
+                        distinct_name = f"Cl{count}"[:4]
+                    elif element == 'BR':
+                        distinct_name = f"Br{count}"[:4]
+                    else:
+                        distinct_name = distinct_name[:4]
+                
+                # Replace atom name (columns 12-16, right-aligned)
+                modified_line = line[:12] + f"{distinct_name:>4}" + line[16:]
+                modified_lines.append(modified_line)
+                modified_count += 1
+            else:
+                modified_lines.append(line)
+        
+        with open(pdb_file, 'w') as f:
+            f.writelines(modified_lines)
+        
+        if modified_count > 0:
+            print(f"Made {modified_count} atom name(s) distinct in {pdb_file}")
+            print(f"Element counts: {dict(element_counts)}")
+        
+        return True
+    except Exception as e:
+        print(f"Error making atom names distinct: {e}")
+        import traceback
+        traceback.print_exc()
+        return False
+
+def sanity_check_ligand_pdb(pdb_file):
+    """Perform sanity checks on ligand PDB file after OpenBabel processing:
+    1. Remove CONECT and MASTER records
+    2. Convert ATOM records to HETATM for consistency
+    3. Make all atom names distinct (C1, C2, O1, O2, H1, H2, etc.) for antechamber compatibility
+    """
+    try:
+        # Step 1: Remove CONECT and MASTER records
+        if not remove_connect_records(pdb_file):
+            return False
+        
+        # Step 2: Convert ATOM to HETATM for consistency
+        if not convert_atom_to_hetatm_in_ligand(pdb_file):
+            return False
+        
+        # Step 3: Make atom names distinct (required by antechamber)
+        if not make_atom_names_distinct(pdb_file):
+            return False
+        
+        print(f"Sanity check completed for {pdb_file}")
+        return True
+    except Exception as e:
+        print(f"Error in sanity check: {e}")
+        return False
+
+def merge_protein_and_ligand(protein_file, ligand_file, output_file, ligand_lines_list=None, ligand_groups=None):
+    """Merge capped protein and corrected ligand(s) with proper PDB formatting
+    
+    Args:
+        protein_file: Path to protein PDB file
+        ligand_file: Path to ligand PDB file (optional, if ligand_lines_list or ligand_groups is provided)
+        output_file: Path to output merged PDB file
+        ligand_lines_list: List of ligand lines (optional, for backward compatibility - single ligand)
+        ligand_groups: List of ligand line groups, where each group is a list of lines for one ligand (for multiple ligands with TER separation)
+    """
+    try:
+        # Read protein file
+        with open(protein_file, 'r') as f:
+            protein_lines = f.readlines()
+        
+        # Get ligand lines - prioritize ligand_groups for multiple ligands
+        if ligand_groups is not None:
+            # Multiple ligands: each group will be separated by TER
+            ligand_groups_processed = ligand_groups
+        elif ligand_lines_list is not None:
+            # Single ligand: wrap in a list for consistent processing
+            ligand_groups_processed = [ligand_lines_list] if ligand_lines_list else []
+        elif ligand_file:
+            # Read ligand file
+            with open(ligand_file, 'r') as f:
+                ligand_lines = f.readlines()
+            # Process ligand file: remove header info (CRYST, REMARK, etc.) and keep only ATOM/HETATM
+            ligand_processed = []
+            for line in ligand_lines:
+                if line.startswith(('ATOM', 'HETATM')):
+                    ligand_processed.append(line)
+            ligand_groups_processed = [ligand_processed] if ligand_processed else []
+        else:
+            ligand_groups_processed = []
+        
+        # Process protein file: remove 'END' and add properly formatted 'TER'
+        protein_processed = []
+        last_atom_line = None
+        for line in protein_lines:
+            if line.strip() == 'END':
+                # Create properly formatted TER card using the last atom's info
+                if last_atom_line and last_atom_line.startswith('ATOM'):
+                    # Extract atom number and residue info from last atom
+                    atom_num = last_atom_line[6:11].strip()
+                    res_name = last_atom_line[17:20].strip()
+                    chain_id = last_atom_line[21:22].strip()
+                    res_num = last_atom_line[22:26].strip()
+                    ter_line = f"TER    {atom_num:>5}      {res_name} {chain_id}{res_num}\n"
+                    protein_processed.append(ter_line)
+                else:
+                    protein_processed.append('TER\n')
+            else:
+                protein_processed.append(line)
+                if line.startswith('ATOM'):
+                    last_atom_line = line
+        
+        # Combine ligands with TER records between each ligand
+        ligand_content = []
+        for i, ligand_group in enumerate(ligand_groups_processed):
+            if ligand_group:  # Only process non-empty groups
+                # Add ligand atoms
+                ligand_content.extend(ligand_group)
+                # Add TER record after each ligand (except the last one, which will be followed by END)
+                if i < len(ligand_groups_processed) - 1:
+                    # Get last atom info from current ligand group to create TER
+                    if ligand_group:
+                        last_ligand_atom = ligand_group[-1]
+                        if last_ligand_atom.startswith(('ATOM', 'HETATM')):
+                            atom_num = last_ligand_atom[6:11].strip()
+                            res_name = last_ligand_atom[17:20].strip()
+                            chain_id = last_ligand_atom[21:22].strip()
+                            res_num = last_ligand_atom[22:26].strip()
+                            ter_line = f"TER    {atom_num:>5}      {res_name} {chain_id}{res_num}\n"
+                            ligand_content.append(ter_line)
+                        else:
+                            ligand_content.append('TER\n')
+        
+        # Combine: protein + TER + ligand(s) with TER between ligands + END
+        merged_content = ''.join(protein_processed) + ''.join(ligand_content) + 'END\n'
+        
+        with open(output_file, 'w') as f:
+            f.write(merged_content)
+        
+        return True
+    except Exception as e:
+        print(f"Error merging files: {str(e)}")
+        import traceback
+        traceback.print_exc()
+        return False
+
+def prepare_structure(pdb_content, options, output_dir="output"):
+    """Main function to prepare structure for AMBER simulation"""
+    try:
+        # Create output directory if it doesn't exist
+        os.makedirs(output_dir, exist_ok=True)
+        
+        # Define all file paths in output directory
+        # Prefer the superimposed completed structure (0_complete_structure.pdb) when it
+        # exists: it has ESMFold/minimized chains aligned to the original frame so that
+        # ligands stay in the same coordinate frame throughout the pipeline.
+        complete_structure_file = os.path.join(output_dir, "0_complete_structure.pdb")
+        original_input_file = os.path.join(output_dir, "0_original_input.pdb")
+        
+        if os.path.exists(complete_structure_file):
+            input_file = complete_structure_file
+            logger.info("Using superimposed completed structure (0_complete_structure.pdb) as input for coordinate-frame consistency with ligands")
+        else:
+            input_file = original_input_file
+            logger.info("Using original input (0_original_input.pdb) as input")
+        
+        user_chain_file = os.path.join(output_dir, "0_user_chain_selected.pdb")
+        protein_file = os.path.join(output_dir, "1_protein_no_hydrogens.pdb")
+        protein_capped_file = os.path.join(output_dir, "2_protein_with_caps.pdb")
+        ligand_file = os.path.join(output_dir, "3_ligands_extracted.pdb")
+        ligand_corrected_file = os.path.join(output_dir, "4_ligands_corrected.pdb")
+        tleap_ready_file = os.path.join(output_dir, "tleap_ready.pdb")
+        
+        # Step 0: Save original input for reference (only if using original input)
+        # If using completed structure, we don't overwrite it
+        if input_file == original_input_file:
+            print("Step 0: Saving original input...")
+            with open(input_file, 'w') as f:
+                f.write(pdb_content)
+        else:
+            # If using completed structure, read it instead of using pdb_content
+            print("Step 0: Using completed structure as input...")
+            with open(input_file, 'r') as f:
+                pdb_content = f.read()
+            # Also save a reference to original input if it doesn't exist
+            if not os.path.exists(original_input_file):
+                print("Step 0: Saving reference to original input...")
+                with open(original_input_file, 'w') as f:
+                    f.write(pdb_content)
+        
+        # Step 0.5: Extract user-selected chains and ligands
+        selected_chains = options.get('selected_chains', [])
+        selected_ligands = options.get('selected_ligands', [])
+        
+        if selected_chains:
+            print(f"Step 0.5a: Extracting selected chains: {', '.join(selected_chains)}")
+            if not extract_selected_chains(pdb_content, user_chain_file, selected_chains):
+                raise Exception("Failed to extract selected chains")
+        else:
+            # No chains selected - raise an error instead of using all chains
+            raise Exception("No chains selected. Please select at least one chain for structure preparation.")
+        
+        if selected_ligands:
+            ligand_names = []
+            for l in selected_ligands:
+                s = f"{l.get('resn', '')}-{l.get('chain', '')}"
+                if l.get('resi'):
+                    s += f" (resi {l.get('resi')})"
+                ligand_names.append(s)
+            print(f"Step 0.5b: Extracting selected ligands: {ligand_names}")
+            if not extract_selected_ligands(pdb_content, ligand_file, selected_ligands):
+                raise Exception("Failed to extract selected ligands")
+        else:
+            print("Step 0.5b: No ligands selected, creating empty ligand file")
+            with open(ligand_file, 'w') as f:
+                f.write('\n')
+        
+        # Step 1: Extract protein only (remove hydrogens) from user-selected chains
+        print("Step 1: Extracting protein without hydrogens from selected chains...")
+        # Read the user-selected chain file
+        with open(user_chain_file, 'r') as f:
+            chain_content = f.read()
+        
+        if not extract_protein_only(chain_content, protein_file):
+            raise Exception("Failed to extract protein")
+        
+        # Step 1b: Merge minimized chains into 1_protein_no_hydrogens.pdb only when the
+        # input is NOT 0_complete_structure. When we use 0_complete_structure, it was
+        # built by rebuild_pdb_with_esmfold, which already incorporates and superimposes
+        # the minimized chains; the raw *_esmfold_minimized_noH.pdb files are in the
+        # minimization frame, so merging them here would break the coordinate frame.
+        if input_file != complete_structure_file:
+            for path in glob.glob(os.path.join(output_dir, "*_chain_*_esmfold_minimized_noH.pdb")):
+                name = os.path.basename(path).replace(".pdb", "")
+                parts = name.split("_chain_")
+                if len(parts) == 2:
+                    chain_id = parts[1].split("_")[0]
+                    replace_chain_in_pdb(protein_file, chain_id, path)
+                    logger.info("Merged minimized chain %s into 1_protein_no_hydrogens.pdb", chain_id)
+        
+        # Step 2: Add capping groups (only if add_ace or add_nme is True)
+        add_ace = options.get('add_ace', True)
+        add_nme = options.get('add_nme', True)
+        
+        if add_ace or add_nme:
+            print("Step 2: Adding ACE and NME capping groups...")
+            if not add_capping_groups(protein_file, protein_capped_file):
+                raise Exception("Failed to add capping groups")
+        else:
+            print("Step 2: Skipping capping groups (add_ace=False, add_nme=False)")
+            print("Using protein without capping - copying to capped file")
+            # Copy protein file to capped file (no capping)
+            shutil.copy2(protein_file, protein_capped_file)
+        
+        # Step 3: Handle ligands (use pre-extracted ligand file)
+        preserve_ligands = options.get('preserve_ligands', True)
+        ligand_present = False
+        ligand_count = 0
+        selected_ligand_count = 0  # Store count from selected_ligands separately
+        
+        # Count selected ligands if provided (before processing)
+        if selected_ligands:
+            # Count unique ligand entities (by residue name, chain, and residue number)
+            unique_ligands = set()
+            for lig in selected_ligands:
+                resn = str(lig.get('resn') or '')
+                chain = str(lig.get('chain') or '')
+                resi = str(lig.get('resi') or '')
+                # Create unique identifier (resi disambiguates when same resn+chain appears multiple times)
+                unique_id = f"{resn}_{chain}_{resi}"
+                unique_ligands.add(unique_id)
+            selected_ligand_count = len(unique_ligands)
+            ligand_count = selected_ligand_count  # Initialize with selected count
+            print(f"Found {selected_ligand_count} unique selected ligand(s)")
+        
+        if preserve_ligands:
+            print("Step 3: Processing pre-extracted ligands...")
+            
+            # Check if ligand file has content (not just empty or newline)
+            with open(ligand_file, 'r') as f:
+                ligand_content = f.read().strip()
+            
+            if ligand_content and len(ligand_content) > 1:
+                ligand_present = True
+                print("Found pre-extracted ligands")
+                
+                # Split ligands into individual files using MDAnalysis (by residue)
+                individual_ligand_files = split_ligands_by_residue(ligand_file, output_dir)
+                # Update ligand_count based on actual split results if not already set from selected_ligands
+                if not selected_ligands or len(individual_ligand_files) != ligand_count:
+                    ligand_count = len(individual_ligand_files)
+                    print(f"Split into {ligand_count} individual ligand file(s)")
+                
+                if ligand_count == 0:
+                    print("Warning: No ligands could be extracted from file")
+                    shutil.copy2(protein_capped_file, tleap_ready_file)
+                else:
+                    print(f"Processing {ligand_count} ligand(s) individually...")
+                    
+                    # Process each ligand: OpenBabel -> sanity check -> final corrected file
+                    corrected_ligand_files = []
+                    for i, individual_file in enumerate(individual_ligand_files, 1):
+                        # OpenBabel output file (intermediate, kept for reference)
+                        obabel_file = os.path.join(output_dir, f"4_ligands_corrected_obabel_{i}.pdb")
+                        # Final corrected file (after sanity checks)
+                        corrected_file = os.path.join(output_dir, f"4_ligands_corrected_{i}.pdb")
+                        
+                        # Use OpenBabel to add hydrogens (write to obabel_file)
+                        if not correct_ligand_with_openbabel(individual_file, obabel_file):
+                            print(f"Error: Failed to process ligand {i} with OpenBabel")
+                            continue
+                        
+                        # Copy obabel file to corrected file before sanity check
+                        shutil.copy2(obabel_file, corrected_file)
+                        
+                        # Perform sanity check on corrected_file: remove CONECT/MASTER, convert ATOM to HETATM, make names distinct
+                        if not sanity_check_ligand_pdb(corrected_file):
+                            print(f"Warning: Sanity check failed for ligand {i}, but continuing...")
+                        
+                        corrected_ligand_files.append(corrected_file)
+                    
+                    if not corrected_ligand_files:
+                        print("Error: Failed to process any ligands")
+                        return {
+                            'error': 'Failed to process ligands with OpenBabel',
+                            'prepared_structure': '',
+                            'original_atoms': 0,
+                            'prepared_atoms': 0,
+                            'removed_components': {},
+                            'added_capping': {},
+                            'preserved_ligands': 0,
+                            'ligand_present': False
+                        }
+                    
+                    # Merge all corrected ligands into a single file for tleap_ready
+                    # Read all corrected ligand files and group them by ligand (for TER separation)
+                    all_ligand_groups = []
+                    for corrected_lig_file in corrected_ligand_files:
+                        with open(corrected_lig_file, 'r') as f:
+                            lig_lines = [line for line in f if line.startswith(('ATOM', 'HETATM'))]
+                            if lig_lines:  # Only add non-empty ligand groups
+                                all_ligand_groups.append(lig_lines)
+                    
+                    # Create combined ligand file (4_ligands_corrected.pdb) for separate download
+                    with open(ligand_corrected_file, 'w') as f:
+                        for i, lig_group in enumerate(all_ligand_groups):
+                            for line in lig_group:
+                                f.write(line if line.endswith('\n') else line + '\n')
+                            if i < len(all_ligand_groups) - 1:
+                                f.write('TER\n')
+                        f.write('END\n')
+                    print(f"Created combined ligand file: {ligand_corrected_file}")
+                    
+                    # Merge protein and all ligands (with TER records between ligands)
+                    if not merge_protein_and_ligand(protein_capped_file, None, tleap_ready_file, ligand_groups=all_ligand_groups):
+                        raise Exception("Failed to merge protein and ligands")
+            elif selected_ligands and ligand_count > 0:
+                # If ligands were selected but file is empty, still mark as present if we have a count
+                ligand_present = True
+                print(f"Ligands were selected ({ligand_count} unique), but ligand file appears empty")
+                # Use protein only since no ligand content found
+                shutil.copy2(protein_capped_file, tleap_ready_file)
+            else:
+                print("No ligands found in pre-extracted file, using protein only")
+                # Copy protein file to tleap_ready
+                shutil.copy2(protein_capped_file, tleap_ready_file)
+        else:
+            print("Step 3: Skipping ligand processing (preserve_ligands=False)")
+            print("Using protein only - copying capped protein to tleap_ready")
+            # Copy protein file to tleap_ready (protein only, no ligands)
+            shutil.copy2(protein_capped_file, tleap_ready_file)
+        
+        # Ensure tleap_ready.pdb exists before proceeding
+        if not os.path.exists(tleap_ready_file):
+            print(f"Error: tleap_ready.pdb was not created. Checking what went wrong...")
+            # Try to create it from protein_capped_file as fallback
+            if os.path.exists(protein_capped_file):
+                print("Creating tleap_ready.pdb from protein_capped_file as fallback...")
+                shutil.copy2(protein_capped_file, tleap_ready_file)
+            else:
+                raise Exception(f"tleap_ready.pdb was not created and protein_capped_file also doesn't exist")
+        
+        # Remove CONNECT records from tleap_ready.pdb (PyMOL adds them)
+        print("Removing CONNECT records from tleap_ready.pdb...")
+        if not remove_connect_records(tleap_ready_file):
+            print("Warning: Failed to remove CONNECT records, but continuing...")
+        
+        # Read the final prepared structure
+        if not os.path.exists(tleap_ready_file):
+            raise Exception("tleap_ready.pdb does not exist after processing")
+        
+        with open(tleap_ready_file, 'r') as f:
+            prepared_content = f.read()
+            
+            # Calculate statistics
+            original_atoms = len([line for line in pdb_content.split('\n') if line.startswith('ATOM')])
+            prepared_atoms = len([line for line in prepared_content.split('\n') if line.startswith('ATOM')])
+            
+            # Calculate removed components
+            water_count = len([line for line in pdb_content.split('\n') if line.startswith('HETATM') and line[17:20].strip() in ['HOH', 'WAT', 'TIP3', 'TIP4', 'TIP5', 'SPC', 'SPCE']])
+            ion_count = len([line for line in pdb_content.split('\n') if line.startswith('HETATM') and line[17:20].strip() in ['NA', 'CL', 'K', 'MG', 'CA', 'ZN', 'FE', 'MN', 'CU', 'NI', 'CO', 'CD', 'HG', 'PB', 'SR', 'BA', 'RB', 'CS', 'LI', 'F', 'BR', 'I', 'PO4', 'PO3', 'H2PO4', 'HPO4', 'H3PO4']])
+            hydrogen_count = len([line for line in pdb_content.split('\n') if line.startswith('ATOM') and line[76:78].strip() == 'H'])
+            
+            # If not preserving ligands, count them as removed
+            ligand_count = 0
+            if not preserve_ligands and ligand_present:
+                # Count ligands from the pre-extracted file
+                with open(ligand_file, 'r') as f:
+                    ligand_lines = [line for line in f if line.startswith('HETATM')]
+                ligand_count = len(set(line[17:20].strip() for line in ligand_lines))
+            
+            removed_components = {
+                'water': water_count,
+                'ions': ion_count,
+                'hydrogens': hydrogen_count,
+                'ligands': ligand_count
+            }
+            
+            # Calculate added capping groups (only if capping was performed)
+            if add_ace or add_nme:
+                # Count unique ACE and NME residues, not individual atoms
+                ace_residues = set()
+                nme_residues = set()
+                
+                for line in prepared_content.split('\n'):
+                    if line.startswith('ATOM') and 'ACE' in line:
+                        # Extract residue number to count unique ACE groups
+                        res_num = line[22:26].strip()
+                        ace_residues.add(res_num)
+                    elif line.startswith('ATOM') and 'NME' in line:
+                        # Extract residue number to count unique NME groups
+                        res_num = line[22:26].strip()
+                        nme_residues.add(res_num)
+                
+                added_capping = {
+                    'ace_groups': len(ace_residues),
+                    'nme_groups': len(nme_residues)
+                }
+            else:
+                added_capping = {
+                    'ace_groups': 0,
+                    'nme_groups': 0
+                }
+            
+            # Count preserved ligands
+            # Priority: 1) selected_ligands count, 2) processed ligand_count, 3) 0
+            if preserve_ligands:
+                if selected_ligand_count > 0:
+                    # Use count from selected_ligands (most reliable)
+                    preserved_ligands = selected_ligand_count
+                    print(f"Using selected ligand count: {preserved_ligands}")
+                elif ligand_present and ligand_count > 0:
+                    # Use count from processing
+                    preserved_ligands = ligand_count
+                    print(f"Using processed ligand count: {preserved_ligands}")
+                elif ligand_present:
+                    # Ligands were present but count is 0, try to count from tleap_ready
+                    # Count unique ligand residue names in tleap_ready.pdb
+                    ligand_resnames = set()
+                    for line in prepared_content.split('\n'):
+                        if line.startswith('HETATM'):
+                            resname = line[17:20].strip()
+                            if resname and resname not in ['HOH', 'WAT', 'TIP', 'SPC', 'NA', 'CL', 'ACE', 'NME']:
+                                ligand_resnames.add(resname)
+                    preserved_ligands = len(ligand_resnames)
+                    print(f"Counted {preserved_ligands} unique ligand residue name(s) from tleap_ready.pdb")
+                else:
+                    preserved_ligands = 0
+            else:
+                preserved_ligands = 0
+            
+            result = {
+                'prepared_structure': prepared_content,
+                'original_atoms': original_atoms,
+                'prepared_atoms': prepared_atoms,
+                'removed_components': removed_components,
+                'added_capping': added_capping,
+                'preserved_ligands': preserved_ligands,
+                'ligand_present': ligand_present,
+                'separate_ligands': options.get('separate_ligands', False)
+            }
+            
+            # If separate ligands is enabled and ligands are present, include ligand content
+            if ligand_present and options.get('separate_ligands', False):
+                with open(ligand_corrected_file, 'r') as f:
+                    result['ligand_content'] = f.read()
+            
+            return result
+        
+    except Exception as e:
+        return {
+            'error': str(e),
+            'prepared_structure': '',
+            'original_atoms': 0,
+            'prepared_atoms': 0,
+            'removed_components': {},
+            'added_capping': {},
+            'preserved_ligands': 0,
+            'ligand_present': False
+        }
+
+def parse_structure_info(pdb_content):
+    """Parse structure information for display"""
+    lines = pdb_content.split('\n')
+    atom_count = 0
+    chains = set()
+    residues = set()
+    water_molecules = 0
+    ions = 0
+    ligands = set()
+    hetatoms = 0
+    
+    # Common water molecule names
+    water_names = {'HOH', 'WAT', 'TIP3', 'TIP4', 'SPC', 'SPCE'}
+    
+    # Common ion names
+    ion_names = {'NA', 'CL', 'K', 'MG', 'CA', 'ZN', 'FE', 'MN', 'CU', 'NI', 'CO', 'CD', 'HG', 'PB', 'SR', 'BA', 'RB', 'CS', 'LI', 'F', 'BR', 'I', 'PO4', 'PO3', 'H2PO4', 'HPO4', 'H3PO4','SO4'}
+    
+    # Common ligand indicators
+    ligand_indicators = {'ATP', 'ADP', 'AMP', 'GDP', 'GTP', 'NAD', 'FAD', 'HEM', 'HEME', 'COA', 'SAM', 'PLP', 'THF', 'FMN', 'FAD', 'NADP', 'UDP', 'CDP', 'TDP', 'GDP', 'ADP', 'ATP'}
+
+    for line in lines:
+        if line.startswith('ATOM'):
+            atom_count += 1
+            chain_id = line[21:22].strip()
+            if chain_id:
+                chains.add(chain_id)
+            
+            res_name = line[17:20].strip()
+            res_num = line[22:26].strip()
+            residues.add(f"{res_name}{res_num}")
+        elif line.startswith('HETATM'):
+            hetatoms += 1
+            res_name = line[17:20].strip()
+            
+            if res_name in water_names:
+                water_molecules += 1
+            elif res_name in ion_names:
+                ions += 1
+            elif res_name in ligand_indicators:
+                ligands.add(res_name)
+
+    # Count unique water molecules
+    unique_water_residues = set()
+    for line in lines:
+        if line.startswith('HETATM'):
+            res_name = line[17:20].strip()
+            res_num = line[22:26].strip()
+            if res_name in water_names:
+                unique_water_residues.add(f"{res_name}{res_num}")
+
+    return {
+        'atom_count': atom_count,
+        'chains': list(chains),
+        'residue_count': len(residues),
+        'water_molecules': len(unique_water_residues),
+        'ions': ions,
+        'ligands': list(ligands),
+        'hetatoms': hetatoms
+    }
+
+def test_structure_preparation():
+    """Test function to verify structure preparation works correctly"""
+    # Create a simple test PDB content
+    test_pdb = """HEADER    TEST PROTEIN
+ATOM      1  N   MET A   1      16.347  37.019  21.335  1.00 50.73           N  
+ATOM      2  CA  MET A   1      15.737  37.120  20.027  1.00 45.30           C  
+ATOM      3  C   MET A   1      15.955  35.698  19.546  1.00 41.78           C  
+ATOM      4  O   MET A   1      16.847  35.123  20.123  1.00 40.15           O  
+ATOM      5  CB  MET A   1      14.234  37.456  19.789  1.00 44.12           C  
+ATOM      6  CG  MET A   1      13.456  36.123  19.234  1.00 43.45           C  
+ATOM      7  SD  MET A   1      12.123  35.456  18.123  1.00 42.78           S  
+ATOM      8  CE  MET A   1      11.456  34.123  17.456  1.00 42.11           C  
+ATOM      9  N   ALA A   2      15.123  35.456  18.789  1.00 40.44           N  
+ATOM     10  CA  ALA A   2      14.456  34.123  18.123  1.00 39.77           C  
+ATOM     11  C   ALA A   2      13.123  33.456  17.456  1.00 39.10           C  
+ATOM     12  O   ALA A   2      12.456  32.123  16.789  1.00 38.43           O  
+ATOM     13  CB  ALA A   2      13.789  33.123  17.123  1.00 38.76           C  
+ATOM     14  N   ALA A   3      12.789  32.456  16.123  1.00 38.09           N  
+ATOM     15  CA  ALA A   3      11.456  31.789  15.456  1.00 37.42           C  
+ATOM     16  C   ALA A   3      10.123  30.456  14.789  1.00 36.75           C  
+ATOM     17  O   ALA A   3       9.456  29.123  14.123  1.00 36.08           O  
+ATOM     18  CB  ALA A   3       9.789  29.456  13.456  1.00 35.41           C  
+ATOM     19  OXT ALA A   3       8.123  28.789  13.456  1.00 35.74           O  
+HETATM   20  O   HOH A   4      20.000  20.000  20.000  1.00 20.00           O  
+HETATM   21  H1  HOH A   4      20.500  20.500  20.500  1.00 20.00           H  
+HETATM   22  H2  HOH A   4      19.500  19.500  19.500  1.00 20.00           H  
+HETATM   23  NA  NA  A   5      25.000  25.000  25.000  1.00 25.00          NA  
+HETATM   24  CL  CL  A   6      30.000  30.000  30.000  1.00 30.00          CL  
+HETATM    1  PG  GTP A 180      29.710  30.132  -5.989  1.00 52.48      A    P  
+HETATM    2  O1G GTP A 180      29.197  28.937  -5.265  1.00 43.51      A    O  
+HETATM    3  O2G GTP A 180      30.881  29.816  -6.827  1.00 63.11      A    O  
+HETATM    4  O3G GTP A 180      30.013  31.278  -5.117  1.00 29.97      A    O  
+HETATM    5  O3B GTP A 180      28.517  30.631  -6.995  1.00 23.23      A    O  
+HETATM    6  PB  GTP A 180      27.017  31.171  -6.766  1.00 29.58      A    P  
+HETATM    7  O1B GTP A 180      26.072  30.050  -6.958  1.00 17.62      A    O  
+HETATM    8  O2B GTP A 180      26.960  31.913  -5.483  1.00 38.76      A    O  
+HETATM    9  O3A GTP A 180      26.807  32.212  -7.961  1.00 13.12      A    O  
+HETATM   10  PA  GTP A 180      26.277  33.726  -8.045  1.00 25.06      A    P  
+HETATM   11  O1A GTP A 180      25.089  33.867  -7.187  1.00 44.06      A    O  
+HETATM   12  O2A GTP A 180      27.427  34.635  -7.843  1.00 23.47      A    O  
+HETATM   13  O5' GTP A 180      25.804  33.834  -9.555  1.00 42.05      A    O  
+HETATM   14  C5' GTP A 180      26.615  33.475 -10.679  1.00 19.97      A    C  
+HETATM   15  C4' GTP A 180      26.219  34.288 -11.894  1.00 14.90      A    C  
+HETATM   16  O4' GTP A 180      24.826  34.017 -12.143  1.00 19.00      A    O  
+HETATM   17  C3' GTP A 180      26.372  35.802 -11.724  1.00  4.96      A    C  
+HETATM   18  O3' GTP A 180      26.880  36.347 -12.936  1.00 44.49      A    O  
+HETATM   19  C2' GTP A 180      24.932  36.243 -11.481  1.00 17.12      A    C  
+HETATM   20  O2' GTP A 180      24.719  37.581 -11.901  1.00 32.45      A    O  
+HETATM   21  C1' GTP A 180      24.069  35.240 -12.240  1.00 16.17      A    C  
+HETATM   22  N9  GTP A 180      22.724  35.005 -11.630  1.00 28.10      A    N  
+HETATM   23  C8  GTP A 180      22.443  34.655 -10.325  1.00 27.05      A    C  
+HETATM   24  N7  GTP A 180      21.168  34.483 -10.079  1.00 33.25      A    N  
+HETATM   25  C5  GTP A 180      20.554  34.737 -11.307  1.00 26.23      A    C  
+HETATM   26  C6  GTP A 180      19.183  34.712 -11.659  1.00 29.31      A    C  
+HETATM   27  O6  GTP A 180      18.205  34.448 -10.957  1.00 40.80      A    O  
+HETATM   28  N1  GTP A 180      19.000  35.036 -13.013  1.00 26.85      A    N  
+HETATM   29  C2  GTP A 180      20.022  35.339 -13.903  1.00 28.70      A    C  
+HETATM   30  N2  GTP A 180      19.627  35.619 -15.147  1.00 44.24      A    N  
+HETATM   31  N3  GTP A 180      21.301  35.367 -13.569  1.00 21.67      A    N  
+HETATM   32  C4  GTP A 180      21.489  35.054 -12.257  1.00 41.91      A    C  
+END
+"""
+    
+    options = {
+        'remove_water': True,
+        'remove_ions': True,
+        'remove_hydrogens': True,
+        'add_ace': True,
+        'add_nme': True,
+        'preserve_ligands': True,
+        'separate_ligands': False,
+        'fix_missing_atoms': False,
+        'standardize_residues': False
+    }
+    
+    print("Testing structure preparation...")
+    result = prepare_structure(test_pdb, options, "output")
+    
+    print("\n=== STATISTICS ===")
+    print(f"Original atoms: {result['original_atoms']}")
+    print(f"Prepared atoms: {result['prepared_atoms']}")
+    print(f"Removed: {result['removed_components']}")
+    print(f"Added: {result['added_capping']}")
+    print(f"Ligands: {result['preserved_ligands']}")
+    print(f"Ligand present: {result['ligand_present']}")
+    
+    print(f"\nTest completed! Check 'output' folder for results:")
+    print("- 1_protein_no_hydrogens.pdb (protein without hydrogens)")
+    print("- 2_protein_with_caps.pdb (protein with ACE/NME caps)")
+    print("- 3_ligands_extracted.pdb (extracted ligands, if any)")
+    print("- 4_ligands_corrected.pdb (corrected ligands, if any)")
+    print("- tleap_ready.pdb (final structure ready for tleap)")
+
+if __name__ == "__main__":
+    test_structure_preparation()

pyproject.toml

@@ -0,0 +1,97 @@
+[build-system]
+requires = ["setuptools>=61.0", "wheel"]
+build-backend = "setuptools.build_meta"
+
+[project]
+name = "ambermdflow"
+version = "0.0.1"
+description = "Web-based MD simulation pipeline with AMBER, ESMFold, docking, and PLUMED"
+readme = "README.md"
+license = {text = "MIT"}
+authors = [
+    {name = "Hemant Nagar", email = "hn533621@ohio.edu"}
+]
+keywords = [
+    "molecular-dynamics",
+    "amber",
+    "md-simulation",
+    "protein-structure",
+    "esmfold",
+    "docking",
+    "autodock-vina",
+    "plumed",
+    "computational-chemistry",
+    "bioinformatics"
+]
+classifiers = [
+    "Development Status :: 4 - Beta",
+    "Environment :: Web Environment",
+    "Framework :: Flask",
+    "Intended Audience :: Science/Research",
+    "License :: OSI Approved :: MIT License",
+    "Operating System :: OS Independent",
+    "Programming Language :: Python :: 3",
+    "Programming Language :: Python :: 3.10",
+    "Programming Language :: Python :: 3.11",
+    "Programming Language :: Python :: 3.12",
+    "Topic :: Scientific/Engineering :: Bio-Informatics",
+    "Topic :: Scientific/Engineering :: Chemistry",
+]
+requires-python = ">=3.10"
+
+# Core dependencies installable via pip
+# Note: Users MUST install these via conda FIRST (not available on PyPI):
+#   conda install -c conda-forge ambertools pymol-open-source vina openbabel rdkit gemmi
+# These conda packages also provide: numpy, pandas, matplotlib (don't override them)
+dependencies = [
+    "flask==2.3.3",
+    "flask-cors==4.0.0",
+    "biopython",
+    "seaborn",
+    "mdanalysis",
+    "gunicorn==21.2.0",
+    "requests",
+    "meeko>=0.7.0",
+    "prody",
+    "numpy<2.0",
+]
+
+[project.optional-dependencies]
+dev = [
+    "pytest>=7.0.0",
+    "pytest-cov>=4.0.0",
+    "black>=23.0.0",
+    "isort>=5.12.0",
+    "flake8>=6.0.0",
+]
+
+[project.urls]
+Homepage = "https://huggingface.co/spaces/hemantn/AmberMDFlow"
+Documentation = "https://github.com/nagarh/AmberMDFlow"
+Repository = "https://github.com/nagarh/AmberMDFlow"
+Issues = "https://github.com/nagarh/AmberMDFlow/issues"
+
+[project.scripts]
+ambermdflow = "ambermdflow.__main__:main"
+
+[tool.setuptools]
+include-package-data = true
+
+[tool.setuptools.packages.find]
+where = ["."]
+include = ["ambermdflow*"]
+
+[tool.setuptools.package-data]
+ambermdflow = [
+    "html/*.html",
+    "css/*.css",
+    "js/*.js",
+]
+
+[tool.black]
+line-length = 100
+target-version = ["py310", "py311", "py312"]
+
+[tool.isort]
+profile = "black"
+line_length = 100

start_web_server.py

@@ -0,0 +1,10 @@
+#!/usr/bin/env python3
+"""
+AmberMDFlow - Entry point when running from project root.
+Uses the ambermdflow package. For installed package: use `ambermdflow` or `python -m ambermdflow`.
+"""
+
+from ambermdflow.app import app
+
+if __name__ == "__main__":
+    app.run(debug=False, host="0.0.0.0", port=7860)