GalaxyDock-DL (linux only)

GalaxyDock-DL is a protein-ligand docking method which utilizes Conformational Space Annealing(CSA) as a sampling algorithm and deep learning-based scoring functions.

Installation Guide (linux only)

1. Install Anaconda if you have not installed it yet.
   
2. Install UCSF Chimera if you have not installed it yet.
   
3. Intallation can be done by running below commands in terminal from main directory location. After git clone, below commands should be run in terminal from main directory location.
   
4. Clone this Git repository
   

$ git clone [email protected]:seoklab/galaxydock_dl.git

Below commands should be run in terminal from main directory location.

5. Create a conda environment using a env.yml file.
   

$ conda env create --file env.yml

6. Activate the conda environment.
   

$ conda activate gd_dl

7. Install source files (gd_dl)
   

$ pip install -e .

When you use GalaxyDock-DL, please make sure you activate the enviroment in terminal first ("conda activate gd_dl").

Usage (linux only)

Below commands should be run in terminal from main directory location.
We recommend checking src/gd_dl/path_setting.py if you want to change path settings.

Running docking

Run docking for a single ligand mol2 file and a protein receptor file without the ligand. (A center coordinate of a docking box (22.5 angstrom^3) is usually set to a coordinate of cognate ligand's geometric center for docking box to include a binding site.)

Random seeds were set to zero, but you can modify random seeds by adding argument

--random_seed <random_seed value>

Default output directory is set to current working directory, but you can modify random seeds by adding argument

--out_dir <location of output directory>

You can change length of docking box by adding argument

--box_size <box size value in angstrom>

$ python scripts/run_gd_dl.py -p <path to protein receptor file(.pdb)> -l <path to ligand file(.mol2)> -x <center x coordinate of a docking box> -y <center y coordinate of a docking box> -z <center z coordinate of a docking box>

Example for 3rsx

$ python scripts/run_gd_dl.py -p ./example/3rsx/3rsx_protein.pdb -l example/3rsx/3rsx_ligand.mol2 -x 69.637 -y 49.989 -z 10.160 --out_dir example/output_dir/

If you want to run docking in terminal from a different directory, you can use bash command with '-d ' below

$ python scripts/run_gd_dl_from_other_directory -d <Path to main directory> -p <path to protein receptor file(.pdb)> -l <path to ligand file(.mol2)> -x <center x coordinate of a docking box> -y <center y coordinate of a docking box> -z <center z coordinate of a docking box>

Output files

• GalaxyDock_fb.mol2: Contains the final output ligand poses, sorted by total score.
• GalaxyDock_fb.E.info: Provides the scores of the final output ligand poses in the final bank, sorted by total score.

For GalaxyDock_fb.E.info:

• The second column (Energy) shows the ranking scores of output poses inferred by neural network scoring functions.
• You can ignore the values in the l_RMSD column, as they only represent RMSD calculated by the Hungarian algorithm between processed input ligand poses and output ligand poses.
• You can also ignore the other columns, which correspond to the values of GalaxyDock BP2 Score energy components multiplied by their weights (ATDK_E: AutoDock Energy, INT_E: AutoDock intra-ligand energy, DS_E: Drug Score, HM_E: Hydrophobic interaction, PLP: PLP score).

GalaxyDock_ib.mol2: Initial ligand conformations in the first bank
box.pdb: Representation of docking box
GalaxyDock_cl.mol2: clustered final output ligand poses sorted by total score

Other output files are used during initialization or sampling and not important after docking is finished.

You can view ligand conformations directly using UCSF chimera
For example,

$ chimera GalaxyDock_fb.mol2

or you can view ligand conformations and protein receptor

$ chimera GalaxyDock_fb.mol2 <path to protein receptor file(.pdb)>

Running docking to test

Running docking for the CASF-2016 core set and PoseBusters test set to reproduce the result using SLURM (Simple Linux Utility for Resource Management).
You can tailor this scripts to work well in your SLURM settings or other linux job schedulers.
Data directory "total_data/" should be downloaded from link and unzipped into a folder in the main directory.

This is for CASF-2016 core set

$ python scripts/multi_run_gd_dl.py prep
$ python scripts/multi_run_gd_dl.py run
$ python scripts/multi_run_gd_dl.py rmsd
$ python scripts/multi_run_gd_dl.py result

This is for CASF-2016 core set using generated molecules generated by CORINA

$ python scripts/multi_run_gd_dl_corina.py prep
$ python scripts/multi_run_gd_dl_corina.py run
$ python scripts/multi_run_gd_dl_corina.py rmsd
$ python scripts/multi_run_gd_dl_corina.py result

This is for PoseBusters set

$ python scripts/posebuster_multi_run_gd_dl.py posebuster prep
$ python scripts/posebuster_multi_run_gd_dl.py posebuster run
$ python scripts/posebuster_multi_run_gd_dl.py posebuster rmsd
$ python scripts/posebuster_multi_run_gd_dl.py posebuster result

This is for PoseBusters set using generated molecules generated by CORINA

$ python scripts/posebuster_multi_run_gd_dl.py posebuster_corina prep
$ python scripts/posebuster_multi_run_gd_dl.py posebuster_corina run
$ python scripts/posebuster_multi_run_gd_dl.py posebuster_corina rmsd
$ python scripts/posebuster_multi_run_gd_dl.py posebuster_corina result

Precompiled Binary

We recommend using the precompiled 'ligdock' binary file located in src/gd_dl/bin/.

Compiling from Source

If you wish to compile it yourself, navigate to the binary_src/ directory by running cd binary_src/ and then execute the following commands (note the ".." at the end of the second command):

$ mkdir -p build && cd build
$ cmake -DCMAKE_BUILD_TYPE=Release -DCMAKE_C_COMPILER=icc -DCMAKE_Fortran_COMPILER=ifort ..
$ cmake --build . --target all -j8

This will generate a new 'ligdock' binary file in the binary_src/bin/ directory.

Ensure that the following compilers are installed before compiling:

• icc (Intel C Compiler)

icc (ICC) 2021.9.0 20230302
Copyright (C) 1985-2023 Intel Corporation.  All rights reserved.

• ifort (Intel Fortran Compiler)

ifort (IFORT) 2021.9.0 20230302
Copyright (C) 1985-2023 Intel Corporation.  All rights reserved.

If you want to replace the original binary file with the new one, you can execute the following command:

$ cp ../bin/ligdock ../../src/gd_dl/bin/ligdock

Citation

If you utilize this code or the models in your research, please cite the following paper:

@article{lee2024galaxydock,
  title={GalaxyDock-DL: Protein--Ligand Docking by Global Optimization and Neural Network Energy},
  author={Lee, Changsoo and Won, Jonghun and Ryu, Seongok and Yang, Jinsol and Jung, Nuri and Park, Hahnbeom and Seok, Chaok},
  journal={Journal of Chemical Theory and Computation},
  year={2024},
  publisher={ACS Publications}
}

License

All code, except for the code in the "binary_src" directory, is licensed under the MIT license. The weights of the neural networks are licensed under the CC BY-NC 4.0 license. Code in the "binary_src" directory is licensed under the CC BY-NC-ND 4.0 license.