luwei0917 / DynamicBind

repo for DynamicBind: Predicting ligand-specific protein-ligand complex structure with a deep equivariant generative model

Setup Environment

Create a new environment for inference. While in the project directory run:

conda create -n dynamicbind python=3.10

Activate the environment

conda activate dynamicbind

Install

conda install pytorch torchvision torchaudio pytorch-cuda=11.7 -c pytorch -c nvidia
conda install -c conda-forge rdkit
conda install pyg  pyyaml  biopython -c pyg
pip install pyg_lib torch_scatter torch_sparse torch_cluster torch_spline_conv -f https://data.pyg.org/whl/torch-2.0.0+cu117.html
pip install e3nn  fair-esm spyrmsd

Create a new environment for structural Relaxation.

conda create --name relax python=3.8

Activate the environment

conda activate relax

Install

conda install -c conda-forge openmm pdbfixer libstdcxx-ng openmmforcefields openff-toolkit ambertools=22 compilers biopython

Checkpoints Download

Download and unzip the workdir.zip containing the model checkpoint form https://zenodo.org/records/10137507

Inference

Dynamic Docking

By default: 40 poses will be predicted, poses will be ranked (rank1 is the best-scoring pose, rank40 the lowest), relax processes are included.

Inputs:

1. Protein (PDB File): protein.pdb
   • Automatically cleaned to remove non-standard amino acids, water molecules, or small molecules.
2. Ligand (CSV File): ligand.csv
   • Must contain a column named 'ligand' listing smiles.
3. Number of Animations:
   • outputs intermediate pkl data, not the final animation PDB. (After --savings_per_complex, default is 40)
4. Frames in Animation/inference_steps:
   • default is 20.

Additional Options:

• --header: Name of the result folder.
• --device: GPU device ID.
• --python: Python environment for inference.
• --relax_python: Python environment for relaxation.
• --num_workers: Number of processes for final output relaxation.

Example Command:

python run_single_protein_inference.py protein.pdb ligand.csv --savings_per_complex 40 --inference_steps 20 --header test --device $1 --python /gxr/luwei/anaconda3/envs/dynamicbind/bin/python --relax_python /gxr/luwei/anaconda3/envs/relax/bin/python

Docking Outputs

The results of the docking step, typically found in the results/test folder, include:

1. Affinity Score for Each Complex: affinity_prediction.csv
2. Pose Score and Conformation of Each Animation: Example files like rank1_ligand_lddt0.63_affinity5.67_relaxed.sdf (where 0.63 is the pose score) and corresponding protein .pdb files.
3. Data for Animation Generation: Such as rank1_reverseprocess_data_list.pkl and rank2_reverseprocess_data_list.pkl.

Movie Generation

Inputs:

1. Data from Docking Output: Indicated by paths like results/test/index0_idx_0/. The notation "1+2" implies that movies for rank1 and rank2 poses are needed.
2. Number of Animations: Specified by the user (default is "1").

Example command for generating movies:

python movie_generation.py results/test/index0_idx_0/ 1+2 --device $1 --python /path/to/dynamicbind/python --relax_python /path/to/relax/python

Outputs:

• Final Animation PDB Files: Located in results/test_1qg8/index0_idx_0/, with files like rank1_receptor_reverseprocess_relaxed.pdb and rank1_ligand_reverseprocess_relaxed.pdb.

High-Throughput Screening (HTS)

Example command for HTS:

python run_single_protein_inference.py protein.pdb ligand.csv --hts --savings_per_complex 3 --inference_steps 20 --header test --device $1 --python /path/to/dynamicbind/python --relax_python /path/to/relax/python

HTS Output files:

• complete_affinity_prediction.csv
• affinity_prediction.csv

Dataset coming soon