GPU-accelerated molecular docking software: Uni-Dock 2

The easiest way to install UniDock2 is via conda:

• Python = 3.10
• CUDA >= 12.0

#You can modify the cuda-version to fit your environment.
conda install unidock2 cuda-version=12.0 -c http://quetz.dp.tech:8088/get/baymax -c conda-forge --no-repodata-use-zst 

git clone https://github.com/dptech-corp/Uni-Dock.git

• CUDA toolkit >= 12.0 (Including nvcc)
• CMake >= 3.27
• C++ compiler
• Pybind11

cd unidock/unidock_engine
pip install .
cd ../..

conda install pyyaml pathos numpy pandas scipy networkx rdkit mdanalysis openbabel pdbfixer openmm cuda-version=12.0 msys_viparr_lpsolve55 ambertools_stable -c http://quetz.dp.tech:8088/get/baymax -c conda-forge --no-repodata-use-zst

pip install .

We recommend all users use our command line functionality. After installation, there will be a command line tool unidock2.

A proper docking inputs should at least contains one receptor file, one or more ligand file, the docking pocket center positions, and the configuration file specifying all the other optional parameters.

• --receptor (-r): Receptor structure file in PDB or DMS format (default: None)
• --ligand (-l): Single ligand structure file in SDF format (default: None)
• --ligand_batch (-lb): Recorded batch text file of ligand SDF file path (default: None)
• --center (-c): Docking box center coordinates (default: [0.0, 0.0, 0.0])
• --configurations (-cf): Uni-Dock2 configuration YAML file recording all other options (default: None)
• --version (-v): Show unidock2 program version
• --help (-h): Show help message and exit

** Note: --ligand or --ligand_batch should have at least one specified.

** Advanced docking engine specified options:

• exhaustiveness: MC candidates count (roughly proportional to time). If given, value for search_mode will be overridden. (default: 512)
• randomize: Whether to randomize input pose before performing the global search. (default: true)
• mc_steps: If given, value for search_mode will be overridden. (default: 20)
• opt_steps: Optimization steps after the global search; -1 to use heuristic strategy. (default: -1)
• refine_steps: Refinement steps after clustering. (default: 5)
• num_pose: Number of the finally generated poses to output. (default: 10)
• rmsd_limit: Minimum RMSD between output poses. (default: 1.0)
• energy_range: Maximum energy difference between output poses and the best pose. (default: 5.0)
• seed: Explicit random seed. (default: 1234567)
• use_tor_lib: True to use torsion library. (default: false)

** Hardware options:

• gpu_device_id: GPU device ID. (default: 0)

** Docking Settings options:

• size_x: Docking box size in the X dimension in Angstrom. (default: 30.0)

• size_y: Docking box size in the Y dimension in Angstrom. (default: 30.0)

• size_z: Docking box size in the Z dimension in Angstrom. (default: 30.0)

• task: screen | score | mc (default: screen) *** screen: The most common mode, perform randomize (if true) + MC (mc_steps) + optimization (opt_steps) + cluster (if true) + refinement (refine_steps) *** score: Only provide scores for input ligands, no searching or optimization *** mc: Only perform pure MC, namely opt_steps=0; no refinement, neither

• search_mode: fast | balance | detail | free. Using recommended settings of exhaustiveness and search steps. (default: balance)

** Docking Preprocessing options:

• template_docking: Specified to true to perform constraint docking mode. (default: false)
• reference_sdf_file_name: Reference molecule SDF file name in constraint docking. (default: null)
• core_atom_mapping_dict_list: Reference to ligand atom mapping dict, please see example case for more detail. (default: null)
• covalent_ligand: Specified to true to perform covalent docking mode. (default: false)
• covalent_residue_atom_info_list: Covalent warhead information for covalent receptor residues, please see example case for more detail. (default: null)
• preserve_receptor_hydrogen: Preserve hydrogen atoms in receptor preparation protocol. (default: false)
• remove_temp_files: Remove intermediate files after docking protocol. (default: true)
• working_dir_name: Docking working directory. (default: .)

The default configuration YAML file is at unidock/unidock_configurations.yaml. In examples folder, there are cases for free docking, constraint docking and covalent docking.

• Free docking

** molecular docking case:

Single ligand docking case. Please see examples/free_docking/molecular_docking, and run

unidock2 -r 1G9V_protein_water_cleaned.pdb -l ligand_prepared.sdf -c 5.122 18.327 37.332 -cf unidock_configurations.yaml

** virtual screening case:

Virtual screening docking case. Please see examples/free_docking/virtual_screening, and run

unidock2 -r 5WIU_protein_cleaned.pdb -l actives_cleaned.sdf -c -18.0 15.2 -17.0 -cf unidock_configurations.yaml

• Constraint docking

For constraint docking, users need to turn on template_docking and specify the file path of reference_sdf_file_name in configuration YAML file.

** automatic atom mapping case:

Use internal algorithms to calculate core atom mapping. Please see examples/constraint_docking/automatic_atom_mapping, and run

unidock2 -r Bace.pdb -lb ligand_batch.dat -c 14.786 -0.626 -1.088 -cf unidock_configurations.yaml

** manual atom mapping case:

Uni-Dock2 also supports customized atom mapping specification in case the default MCS algorithm does not perfroms well. To do this, specify core_atom_mapping_dict_list in the configuration YAML file, please refer to examples/constraint_docking/manual_atom_mapping/unidock_configurations.yaml for example usage. Please see examples/constraint_docking/manual_atom_mapping, and run

unidock2 -r protein.pdb -l ligand.sdf -c 9.028 0.804 21.789 -cf unidock_configurations.yaml

• Covalent docking

For covalent docking, users need to turn on covalent_ligand and specify the covalent residue information covalent_residue_atom_info_list in the configuration YAML file. The covalent_residue_atom_info_list is a list consist of 3 tuple, specifying protein residue information of heavy atoms from warhead to covalent bond starting atom, and covalent ending atom. Please see examples/covalent_docking/unidock_configurations.yaml for example usage. Please see examples/covalent_docking, and run

unidock2 -r 1EWL_prepared.pdb -l covalent_mol.sdf -c 8.411 13.047 6.811 -cf unidock_configurations.yaml