DSDPFlex: Flexible-Receptor Docking with GPU Acceleration

DSDPFlex is a GPU-accelerated flexible-receptor docking program derived from DSDP (Deep Site and Docking Pose). Similar to AutoDock Vina, it supports selective side-chain flexibility during docking. A flexible docking process is typically completed in ~1 s with DSDPFlex. Learn more in our paper (DOI: 10.1021/acs.jcim.4c01715 )

Installation

DSDPFlex runs on a Linux machine (tested on Ubuntu 22.04 and 20.04).

A GPU with CUDA is required. NVCC is used for compilation. Please install Cuda Toolkit and make sure it is in the system PATH variable. (check with nvcc --version)

Note

The CUDA version needs to be compatible with the GPU architecture and gcc/g++ version.

An example version we used is cuda_11.6 with gcc_9.4.0 (tested on NVIDIA RTX 3070Ti & RTX A4000). If an older GPU (former to the GTX/RTX Turing) is used on your computer, the option -arch=sm_70 in Makefile needs to be modified to a compatible one.

Clone this repository.

git clone https://github.com/PKUGaoGroup/DSDPFlex.git
cd DSDPFlex

Install DSDPFlex. Suppose you are at the root of this repository,

cd DSDPFlex_v0.2
make clean && make
cp DSDPflex ../bin
cd ..

A binary named DSDPflex will be compiled. You can add it to the PATH variable by adding this line to ~/.bashrc (if using Bash)

export PATH=/path/to/DSDPFlex/bin:$PATH

so that DSDPflex can be directly called from the command line.

Using DSDPFlex

Flexible docking with DSDPFlex.

(If the flexible receptor parts are not needed, DSDP will work better.)

For a ligand-receptor pair:

./DSDPflex --ligand ligand.pdbqt \
--protein receptor_rigid.pdbqt \
--flex receptor_flex.pdbqt \
--box_min x y z \
--box_max x y z \
--exhaustiveness 384 --search_depth 40 --top_n 1 \
--out ligand_out.pdbqt \
--out_flex flex_out.pdbqt \
--log dsdp_out.log

Input: DSDPFlex supports .pdbqt formatted input files, which can be prepared with AutoDockTools.

--ligand ligand file name (required)
--protein protein rigid part (required)
--flex protein flexible part file (required for flexible docking)

Output:

--out the output file of ligand poses (default=DSDP_out.pdbqt)
--out_flex the output file of flexible side chain poses (default=DSDP_out_flex.pdbqt)
--log the log file name (default=DSDP_out.log)
--top_n the top-N ranking results will be exported (defualt=10)

Search space: The search space information needs to be provided. The search box specifies the (known) binding site. The ligand box is used for restricting ligand translation, which can be a smaller box.

--box_min x y z minima of the search box (in Angstrom)
--box_max x y z maxima of the search box
--ligbox_min x y z minima of the ligand box
--ligbox_max x y z maxima of the ligand box

Search settings: Can be manually adjusted. The default settings generally work well.

--exhaustiveness the number of sampling threads, default=384
--search_depth the number of sampling iterations of each thread, default=40

Use --help to see more details.

Using the ligand batch mode

A batch mode is designed for docking multiple ligands to a single receptor (e.g. in a virtual screening scenario).

./DSDPflex --ligand_batch batch_list --protein receptor_rigid.pdbqt --flex receptor_flex.pdbqt ...

The batch_list should be a text file, like

ligand_0.pdbqt out_0.pdbqt out_flex_0.pdbqt
ligand_1.pdbqt out_1.pdbqt out_flex_1.pdbqt
...

It will replace the --ligand, --out, and --out_flex options. Each file name should be a valid file path. The protein files (--protein & --flex) still need to be specified.

Using DSDPFlex_pyTools

We provide a Python interface for calling DSDPFlex and related tools. It is recommended to run rescoring with this DSDPFlex_pyTools. More functions can be implemented in the future.

We recommend setting up the Python environment with conda.

conda create -n DSDPFlex_py
conda activate DSDPFlex_py

Then you can install the DSDPFlex_pyTools package by the following command:

cd ./DSDPFlex_pyTools
python ./setup.py install

Then the command DSDPflex-py will be available in the current python environment.

Rescoring with GNINA

Before using DSDPflex-py, make sure that DSDPflex is in your system path (see Installation). To use GNINA, please install GNINA and add it to the PATH variable.

To use DSDPflex-py:

DSDPflex-py --ligand ... --protein ... --rescore gnina

(the other options are the same as DSDPflex.) DSDPflex-py will call gnina for rescoring after docking by DSDPflex. By default, top-20 poses are rescored, and the output files will be named *_rescored.pdbqt

Other rescoring methods might be implemented in the future.

Run DSDPFlex on APOBind core

The 229 systems within APOBind dataset, used for evaluation in the paper, are provided in test/apobind_prepared.

To run this test:

cd ./test
sh ./run_apobind.sh

DSDPFlex will perform docking on all systems. We used sPyRMSD to calculate RMSDs in the paper.

Advanced Options of DSDPFlex

There are advanced options in DSDPflex that allow manual adjustment or further development of the program.

--no_norm let the program not normalize the intra-protein score (i.e. using the original Vina score, see more in the paper)
--norm_param <float> modify the normalization parameter $c$ the re-weighting factor of the intra-protein score ($\gamma$) will be $$\gamma = c\times \min(f_\text{ligand} / f_\text{flex}, 1)$$ default $c = 1/2$
--rand_init_flex randomly initialize flexible side-chain conformations. By default, DSDPflex keeps the initial side-chain conformations.
--rank_ligand_only consider only ligand-related scores when ranking (&output) the poses.

Cite this work

DSDPFlex: Flexible-Receptor Docking with GPU Acceleration.
Chengwei Dong, Yu-Peng Huang, Xiaohan Lin, Hong Zhang, and Yi Qin Gao
Journal of Chemical Information and Modeling Article ASAP
DOI: 10.1021/acs.jcim.4c01715

LICENSE

Licensed under GNU AFFERO GENERAL PUBLIC LICENSE (Version 3), you may not use this file except in compliance with the License. Any commercial use is not permitted.

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