unigbsa 0.1.7

Uni-GBSA: An Automatic Workflow to Perform MM/GB(PB)SA Calculations for Virtual Screening==============================================================================[Briefings in Bioinformatics]## BackgroundCalculating the binding free energy of a ligand to a protein receptor is a crucial goal in drug discovery. Molecular mechanics/Generalized-Born (Poisson-Boltzmann) surface area (MM/GB(PB)SA), which balances accuracy and efficiency, is one of the most widely used methods for evaluating ligand binding free energies in virtual screening. Uni-GBSA is an automatic workflow to perform MM/GB(PB)SA calculations. It includes several functions, including but not limited to topology preparation, structure optimization, binding free energy calculation, and parameter scanning for MM/GB(PB)SA calculations. Additionally, it has a batch mode that allows the evaluation of thousands of molecules against one protein target simultaneously, enabling its application in virtual screening.## Install### Install via CondaTo run uni-GBSA, you need to install several third-party softwares including acpype, gmx_MMPBSA, lickit, etc.Bashconda create -n gbsa -c conda-forge acpype openmpi mpi4py gromacs "gmx_mmpbsa>=1.5.6"conda activate gbsapip install unigbsa lickit### Install by docker imagesYou can also build a docker image using this file or pull from the docker hub docker pull dockerymh/unigbsa````PlaintextFROM continuumio/miniconda3# 1. create an environmentSHELL ["/bin/bash", "-c"]RUN conda create -n gbsa -c conda-forge acpype openmpi mpi4py gromacs "gmx_MMPBSA>=1.5.6" \&& echo 'conda activate gbsa' >> ~/.bashrc \&& rm -rf /opt/conda/pkgs/* # 2. install unigbsaRUN source ~/.bashrc \ && pip install unigbsa lickit \&& rm -rf ~/.cache/*```## Usage & Example### Usage```bash$ unigbsa-pipeline -husage: unigbsa-pipeline [-h] -i RECEPTOR [-l LIGAND [LIGAND ...]] [-c CONFIG] [-d LIGDIR] [-f PBSAFILE] [-o OUTFILE] [-validate] [-nt THREADS] [--decomp] [--verbose] [-v]MM/GB(PB)SA Calculation. Version: 0.1.6optional arguments: -h, --help show this help message and exit -i RECEPTOR Input protein file in pdb format. -l LIGAND [LIGAND ...] Ligand files to calculate binding energy for. -c CONFIG Config file, default: /home/jochem/miniforge3/envs/gbsa_test/lib/python3.9/site-packages/unigbsa/data/default.ini -d LIGDIR Directory containing many ligand files. file format: .mol or .sdf -f PBSAFILE gmx_MMPBSA input file. default=None -o OUTFILE Output file. -validate Validate the ligand file. default: False -nt THREADS Set number of threads to run this program. --decomp Decompose the free energy. default:False --verbose Keep all the files. -v, --version show program's version number and exit```### Example```bash$ unigbsa-pipeline -i example/1ceb/1ceb_protein.pdb -l example/1ceb/1ceb_ligand.sdf -o BindingEnergy.csv07/07/2024 15:56:01 PM - INFO - Build protein topology.07/07/2024 15:56:02 PM - INFO - Build ligand topology: 1ceb_ligand07/07/2024 15:56:03 PM - INFO - Running energy minimization: 1ceb_ligand07/07/2024 15:56:04 PM - INFO - Run the MMPB(GB)SA.07/07/2024 15:56:12 PM - INFO - Clean the results.================================================================================Results: Energy.csv Dec.csvFrames mode delta_G(kcal/mole) 1 gb -20.1781 ```## Other ToolsThis packge contains several commands: unigbsa-scan, unigbsa-pipeline, unigbsa-traj, unigbsa-pbc, unigbsa-buildtop, unigbsa-buildsys, unigbsa-md.### unigbsa-scan>Perform an automatic parameter optimization prior to production MM/GB(PB)SA calculations.```Bash$ unigbsa-scan -husage: unigbsa-scan [-h] [-i RECEPTOR] [-pd PROTDIR] [-l LIGAND [LIGAND ...]] [-ld LIGDIR] -e E -c PARASFILE [-o OUTDIR] [-nt THREADS] [--verbose]Perform an automatic parameter optimization prior to production MM/GB(PB)SA calculations.optional arguments: -h, --help show this help message and exit -i RECEPTOR Input protein file in pdb format. -pd PROTDIR Directory containing many protein files. file format: .pdb -l LIGAND [LIGAND ...] Ligand files to calculate binding energy. -ld LIGDIR Directory containing many ligand files. file format: .mol or .sdf -e E Experiment data file. -c PARASFILE Parameters to scan -o OUTDIR Output directory. -nt THREADS Set number of threads to run this program. --verbose Keep all the files.```>Example```Bashunigbsa-scan -i example/scan/protein.pdb -ld example/scan/ -e example/scan/ligands.csv -c example/scan/scan.json -o scan-demo -nt 4```### unigbsa-pipeline>A simple, automatic pipeline to perform MM/GB(PB)SA calculations. You only need to provide a protein file (in the PDB format) and ligand files (in the MOL or SDF format). This function will perform an energy minimization then calculate the PBSA/GBSA values for the each input ligand.* If you want perform energy minimization or MD simulation for the complex automatically, use the ``unigbsa-pipeline`` function.```Bash$ unigbsa-pipeline -husage: unigbsa-pipeline [-h] -i RECEPTOR [-l LIGAND [LIGAND ...]] [-c CONFIG] [-d LIGDIR] [-f PBSAFILE] [-o OUTFILE] [-validate] [-nt THREADS] [--decomp] [--verbose] [-v]MM/GB(PB)SA Calculation. Version: 0.1.6optional arguments: -h, --help show this help message and exit -i RECEPTOR Input protein file in pdb format. -l LIGAND [LIGAND ...] Ligand files to calculate binding energy for. -c CONFIG Config file, default: default.ini -d LIGDIR Directory containing many ligand files. file format: .mol or .sdf -f PBSAFILE gmx_MMPBSA input file. default=None -o OUTFILE Output file. -validate Validate the ligand file. default: False -nt THREADS Set number of threads to run this program. --decomp Decompose the free energy. default:False --verbose Keep all the files. -v, --version show program's version number and exit```You can change the parameters for the MM/GB(PB)SA calculations by providing a config file (default.ini). ```; parameters for simulation[simulation]; input pose process method: ; input - just use input pose to calculation; em - run a simple energy minimizaion for the input poses; md - run a md simulation for the input posesmode = em; simulation box type: triclinic, cubic, dodecahedron, octahedronboxtype = triclinic; Distance between the solute and the simulation boxboxsize = 0.9; Specify salt concentration (mol/liter). This will add sufficient ions to reach up to the specified concentrationconc = 0.15; number of md simulation stepsnsteps = 500000; number of equilibrium simulation(nvt, npt) stepseqsteps = 50000; number of structure to save for the md simulationnframe = 100; protein forcefield (gromacs engine)proteinforcefield = amber03; ligand forcefield (acpype engine)ligandforcefield = gaff; ligand charge method: bcc, gasligandCharge = bcc; parameters for PBSA/GBSA calculation, support all the gmx_MMPBSA parameters[GBSA]; calculation namesys_name = GBSA; calculation mode, Separated by commas. gb,pb,decompositionmodes = gb; best parameters for PBSA/GBSA calculations obtained from Wang, Ercheng, et al. Chemical reviews 119.16 (2019): 9478-9508.igb = 2indi = 4.0exdi = 80.0```### unigbsa-traj>Perform a PBSA/GBSA calculation of a complex from a MD trajectory. Note: you need to prepare a gromacs index.ndxfile which contains two groups namedRECEPTORandLIGAND`.$ unigbsa-traj -husage: unigbsa-traj [-h] -i INP -p TOP -ndx NDX [-m MODE [MODE ...]] [-f MMPBSAFILE] [-t TRAJ] [-nt THREADS] [-D] [-v]Free energy calcaulation by MM/GB(PB)SA method.optional arguments: -h, --help show this help message and exit -i INP A pdb file or a tpr file for the trajectory. -p TOP Gromacs topol file for the system. -ndx NDX Gromacs index file, must contain receptor and ligand group. -m MODE [MODE ...] MM/GB(PB)SA mode -f MMPBSAFILE Input MM/GB(PB)SA file -t TRAJ A trajectory file containing many structure frames. File format: xtc, pdb, gro... -nt THREADS Set number of threads to run this program. -D DEBUG model, keep all the files. -v, --version show program's version number and exit### unigbsa-buildtop>Topology preparation for a protein receptor and ligand(s) using gromacs.Bash$ unigbsa-buildtop -husage: unigbsa-buildtop [-h] [-p PROTEIN] [-l LIGAND] [-pf PROTFORCE] [-lf {gaff,gaff2}] [-o OUTDIR] [-c] [-nt THREADS] [-verbose] [-v]Build topology file for input file.optional arguments: -h, --help show this help message and exit -p PROTEIN Protein file or directory to build topology. -l LIGAND Ligand file or directory to build topology. -pf PROTFORCE Protein forcefield. -lf {gaff,gaff2} Ligand forcefield: gaff or gaff2. -o OUTDIR The output directory. -c Combine the protein and ligand topology. Suppport for one protein and more ligands. default:True -nt THREADS Number of threads to run this simulation. -verbose Keep the directory or not. -v, --version show program's version number and exit### unigbsa-buildsys>Build a simulation box for a protein-ligand complex.```bash$ unigbsa-buildsys -husage: unigbsa-buildsys [-h] -p PROTEIN [-l LIGAND] [-pf PROTFORCE] [-lf {gaff,gaff2}] [-bt BOXTYPE] [-box BOX BOX BOX] [-d D] [-conc CONC] [-o OUTDIR] [-nt THREADS] [-v]Build MD simulation for input file.optional arguments: -h, --help show this help message and exit -p PROTEIN Protein file for the simulation. -l LIGAND Ligand file or directory for the simulation. -pf PROTFORCE Protein forcefield. -lf {gaff,gaff2} Ligand forcefield: gaff or gaff2. -bt BOXTYPE Simulation box type, default: triclinic -box BOX BOX BOX Simulation box size. -d D Distance between the solute and the box. -conc CONC Specify salt concentration (mol/liter). default=0.15 -o OUTDIR The output directory. -nt THREADS Number of threads to run this simulation. -v, --version show program's version number and exit```### unigbsa-md>Run a MD simulation of a protein-ligand complex.```Bash$ unigbsa-md -husage: unigbsa-md [-h] -p PROTEIN [-l LIGAND] [-pf PROTFORCE] [-lf {gaff,gaff2}] [-bt BOXTYPE] [-box BOX BOX BOX] [-d D] [-conc CONC] [-o OUTDIR] [-nsteps NSTEP] [-nframe NFRAME] [-nt THREADS] [-verbose] [-v]Run MD simulation for input file.optional arguments: -h, --help show this help message and exit -p PROTEIN Protein file for the simulation. -l LIGAND Ligand file or directory for the simulation. -pf PROTFORCE Protein forcefield. -lf {gaff,gaff2} Ligand forcefield: gaff or gaff2. -bt BOXTYPE Simulation box type, default: triclinic -box BOX BOX BOX Simulation box size. -d D Distance between the solute and the box. -conc CONC Specify salt concentration (mol/liter). default=0.15 -o OUTDIR The output directory. -nsteps NSTEP Simulation steps. default:2500 -nframe NFRAME Number of frames to save for the xtc file. default:100 -nt THREADS Number of threads to run this simulation. -verbose Keep all the files in the simulation. -v, --version show program's version number and exit```### unigbsa-pbc>Process PBC condition for a MD trajectory.```Bash$ unigbsa-pbc -husage: unigbsa-pbc [-h] -s TPR -f XTC [-o OUT] [-n NDX] [-v]Auto process PBC for gromacs MD trajectory.optional arguments: -h, --help show this help message and exit -s TPR TPR file generated from gromacs or coordinate file. -f XTC Trajectory file to process PBC. -o OUT Results file after processed PBC. -n NDX Index file contains the center and output group. -v, --version show program's version number and exit```### More Examples* Perform a MM/GB(PB)SA calculation on a ligand file with a protein receptor with unigbsa-pipeline``````Bashunigbsa-pipeline -i ./example/2fvy/protein.pdb -l ./example/2fvy/BGC.mol2````* Perform a MM/GB(PB)SA calculation of a complex from a MD trajectory with unigbsa-trajBashunigbsa-traj -i example/3f/complex.pdb -p example/3f/complex.top -ndx example/3f/index.ndx -m pb gb -t example/3f/complex.pdb```* Build topology for a protein receptor and a ligand using gromacs. ``unigbsa-buildtopbashunigbsa-buildtop -p example/2fvy/protein.pdb -pf amber99sb -o topol # build gromacs topology for a single proteinunigbsa-buildtop -p example/2fvy/protein.pdb -pf amber99sb -l example/2fvy/BGC.mol2 -lf gaff -o 2fvy_topol -c # build gromacs topology for protein and ligand complex```* Build a simulation system with ``unigbsa-buildsys``* Run a MD simulation with ``unigbsa-md``* Process the PBC condition of a MD trajectory with ``unigbsa-pbc``## Citation```plaintextMaohua Yang and others, Uni-GBSA: an open-source and web-based automatic workflow to perform MM/GB(PB)SA calculations for virtual screening, Briefings in Bioinformatics, 2023;, bbad218, https://doi.org/10.1093/bib/bbad218.```