Uni-Dock2

GPU-accelerated molecular docking software: Uni-Dock 2

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Installation

Conda Installation

The easiest way to install UniDock2 is via conda:

Prerequisites * Python = 3.10 * CUDA >= 12.0

```sh

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 ```

Manual Build

sh git clone https://github.com/dptech-corp/Uni-Dock2.git

Step 1. Build unidock_engine

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

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

Step 2. Build unidock_processing

sh conda install pyyaml pathos numpy pandas scipy networkx rdkit mdanalysis 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 .

Verify Installation

sh unidock2 --version

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Usage

Check unidock2 usage by unidock2 --help. Basically there are two types of task: molecular docking and protein preparation. This document focuses on the docking task, since protein preparation is similar and we recommend consulting the help information.

Configuration File

A configuration YAML file is all you need to run docking tasks: unidock2 docking -cf your_config.yaml Use unidock2 docking --help to check how to write the YAML file.

ATTENTION If a parameter is not written in the YAML, the default value of the parameter will be used (e.g., size=[30, 30, 30]). Carefully check the default values in the help information.

Command Line Parameters

Core parameters in the YAML file have command line equivalents. Command line inputs will override YAML values: sh -r RECEPTOR, --receptor RECEPTOR Receptor structure file in PDB or DMS format -l LIGAND, --ligand LIGAND Single ligand structure file in SDF format -lb LIGAND_BATCH, --ligand_batch LIGAND_BATCH Recorded batch text file of ligand SDF file path -c center_x center_y center_z, --center center_x center_y center_z Docking box center coordinates -o OUTPUT_DOCKING_POSE_SDF_FILE_NAME, --output_docking_pose_sdf_file_name OUTPUT_DOCKING_POSE_SDF_FILE_NAME Output docking pose SDF file name

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Quick Docking Tutorial

A typical docking input includes at least one receptor file, one ligand file, docking pocket center coordinates and box size. Example cases could be found in the examples folder.

1. Free Docking

The ligand molecule can translate, rotate and adjust torsion angles within the docking box.

1.1. Molecular Docking

Single receptor vs. single ligand.

cd examples/free_docking/molecular_docking

YAML Write the test.yaml as yaml Required: receptor: 5WIU_protein_water_cleaned.pdb ligand: actives_cleaned.sdf center: [5.122, 18.327, 37.332] Settings: box_size: [30.0, 30.0, 30.0] and run unidock2 docking -cf test.yaml.

Command Line You can also use command line parameters: sh unidock2 docking -r 1G9V_protein_water_cleaned.pdb -l ligand_prepared.sdf -c 5.122 18.327 37.332

1.2. Virtual Screening

Single receptor vs. multiple ligands.

1.2.1 Single SDF with Multiple Ligands

sh cd examples/free_docking/virtual_screening

YAML Write the test.yaml as yaml Required: receptor: 5WIU_protein_cleaned.pdb ligand: actives_cleaned.sdf # One SDF file contains multiple ligands center: [5.122, 18.327, 37.332] Settings: box_size: [30.0, 30.0, 30.0] and run unidock2 docking -cf test.yaml.

Command Line You can also use command line parameters: sh unidock2 -r 5WIU_protein_cleaned.pdb -l actives_cleaned.sdf -c -18.0 15.2 -17.0

1.2.2 Multiple SDF Files

Use an index file to record SDF file names, like test.index sh 1.sdf 2.sdf 3.sdf 4.sdf

YAML Then write the test.yaml as yaml Required: receptor: 5WIU_protein_cleaned.pdb ligand_batch: test.index center: [5.122, 18.327, 37.332] Settings: box_size: [30.0, 30.0, 30.0] and run unidock2 docking -cf test.yaml.

Command Line sh unidock2 -r 5WIU_protein_cleaned.pdb -lb test.index -c -18.0 15.2 -17.0

1.2.3 Combined Input

SDF files from both ligand and ligand_batch sources will be processed.

2. Template Docking

When using a reference molecule, the query ligand will align to it. You need to set template_docking = true.

After alignment and during docking, the query can't translate or rotate. Only non-core torsions can be adjusted.

2.1 Automatic Atom Mapping

Uni-Dock2 will automatically compute the atom mapping. cd examples/constraint_docking/automatic_atom_mapping

YAML Then write the test.yaml as yaml Required: receptor: Bace.pdb ligand_batch: batch.dat center: [14.786, -0.626, -1.088] Settings: box_size: [30.0, 30.0, 30.0] Preprocessing: template_docking: true reference_sdf_file_name: reference.sdf and run unidock2 docking -cf test.yaml

2.2 Custom Atom Mapping

Specify core_atom_mapping_dict_list in the YAML file.

ATTENTION If length of core_atom_mapping_dict_list is smaller than ligand count, the remaining ligands will use automatically computed atom mapping instead.

cd examples/constraint_docking/manual_atom_mapping

YAML Then write the test.yaml as yaml Required: receptor: protein.pdb ligand: ligand.sdf center: [9.028, 0.804, 21.789] Settings: box_size: [30.0, 30.0, 30.0] Preprocessing: template_docking: true reference_sdf_file_name: reference.sdf core_atom_mapping_dict_list: [{'0': 14, '1': 15, '10': 11, '11': 12, '12': 13, '16': 1, '17': 2, '18': 3, '19': 4, '20': 6, '21': 7, '22': 8, '23': 9, '24': 20, '25': 21, '27': 27, '6': 24, '7': 0, '8': 5, '9': 10}] and run unidock2 docking -cf test.yaml

3. Covalent Docking

For covalent docking, please set covalent_ligand = true and specify covalent_residue_atom_info_list. covalent_residue_atom_info_list is a list of 3 tuple, specifying protein residue information of warhead, covalent bond starting atom, and covalent ending atom.

ATTENTION Input files MUST be prepared using Hermite ligand preparation.

cd examples/covalent_docking/

YAML Then write the test.yaml as yaml Required: receptor: 1EWL_prepared.pdb ligand: covalent_mol.sdf center: [8.411, 13.047, 6.811] Settings: box_size: [30.0, 30.0, 30.0] Preprocessing: covalent_ligand: true covalent_residue_atom_info_list: [["", "CYX", 25, "CA"], ["", "CYX", 25, "CB"], ["", "CYX", 25, "SG"]] and run unidock2 docking -cf test.yaml