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DualStrike Docking Simulation

This project performs a molecular docking simulation between the NPM-ALK fusion protein and the novel dual-site inhibitor, DualStrike, using AlphaFold 3 for protein structure prediction and SwissDock for docking. It is for Siraj Raval's video on Youtube, and HPC-AI compute cloud was used for affordability.

Table of Contents

Prerequisites

Before you begin, ensure you have the following installed:

  • Python 3.7 or higher
  • pip (Python package installer)
  • The following Python packages:
    • Biopython
    • RDKit
    • NumPy
    • pandas
    • matplotlib
    • requests

Note: RDKit installation can be non-trivial on some systems. Follow the official installation guide: RDKit Install

Setup Instructions

  1. Clone or Download the Repository:

    git clone https://github.com/yourusername/dualstrike_docking.git
cd dualstrike_docking

  2. Create a Virtual Environment (Optional but Recommended):

 python3 -m venv venv
 source venv/bin/activate  # On Windows use: venv\Scripts\activate
  1. Install the Required Packages: 
    pip install biopython rdkit pandas numpy matplotlib requests
    Note: If you encounter issues installing RDKit via pip, refer to the official installation guide.

Running the Script

Making the Script Executable (Optional)

chmod +x dualstrike_docking.py

Running Options

# Standard execution
python dualstrike_docking.py

# If made executable
./dualstrike_docking.py

Detailed Steps

1. Prepare the NPM-ALK Fusion Protein Sequence

  • Script automatically writes the sequence to npm_alk_fusion.fasta
  • No manual action required

2. Submit Sequence to AlphaFold

Note: Manual submission required due to lack of public API

  1. Visit AlphaFold Protein Server website
  2. Upload generated npm_alk_fusion.fasta
  3. Submit and await completion
  4. Download predicted structure (CIF format)
  5. Save as npm_alk_fusion.cif in script directory

3. Process AlphaFold Output

  • Script converts CIF to PDB format
  • Ensure npm_alk_fusion.cif is in script directory
  • Generates npm_alk_fusion.pdb

4. Prepare DualStrike Inhibitor Structure

  • Uses RDKit for 3D structure generation
  • Creates dualstrike.sdf from SMILES notation

5. Perform SwissDock Docking

Note: Manual submission required

  1. Visit SwissDock Web Interface
  2. Upload:
    • Receptor: npm_alk_fusion.pdb
    • Ligand: dualstrike.sdf
  3. Configure parameters (defaults acceptable)
  4. Submit and note Job ID
  5. Wait for completion

6. Analyze and Visualize Results

  1. Download results archive from SwissDock
  2. Extract to folder (e.g., SwissDock_results)
  3. Provide results folder path when prompted
  4. Script generates statistics and visualizations

Understanding the Outputs

Binding Energy Statistics

  • Provides descriptive statistics:
    • Mean
    • Standard deviation
    • Minimum/Maximum values

Visualization

  • Histogram of binding energy distribution

Output Files

  • npm_alk_fusion.fasta: Fusion protein sequence
  • npm_alk_fusion.pdb: Protein structure
  • dualstrike.sdf: Inhibitor structure
  • Results folder: Contains all SwissDock output files

Troubleshooting

RDKit Installation Issues

# Alternative installation via conda
conda create -c conda-forge -n my-rdkit-env rdkit
conda activate my-rdkit-env

Common Issues

  • Missing Files/Incorrect Paths

    • Verify file names and locations
    • Check paths when prompted

  • Script Errors

    • Check for missing dependencies
    • Verify file formats

  • Docking Issues

    • Review SwissDock error messages
    • Verify file formatting

References

Contact Information

Disclaimer

This script and associated instructions are provided for educational and research purposes. The DualStrike inhibitor is a hypothetical molecule used for demonstration. Always ensure compliance with all relevant laws, regulations, and ethical guidelines when conducting research.

License

MIT LICENSE