Package: unigbsa
Uni-GBSA: An Automatic Workflow to Perform MM/GB(PB)SA Calculations for Virtual Screening==============================================================================[Briefings in Bioinformatics]## BackgroudCalculating 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. It also 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 by 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 gromacsconda activate gbsapip install unigbsa gmx_MMPBSA>=1.5.6 lickit### Install by docker imagesYou can also build a docker image using this file or pull from the docker hubdocker pull dockerymh/unigbsa````PlaintextFROM continuumio/miniconda3# 1. create a enveriomentSHELL ["/bin/bash", "-c"]RUN conda create -n gbsa -c conda-forge acpype openmpi mpi4py gromacs \&&  echo 'conda activate gbsa' >> ~/.bashrc \&&  rm -rf /opt/conda/pkgs/* # 2. install unigbsaRUN source ~/.bashrc \ &&  pip install unigbsa gmx_MMPBSA>=1.5.6 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] [-nt THREAD]                        [--decomp] [--verbose] [-v]GBSA Calculation. Version: 0.0.9_devoptions:  -h, --help            show this help message and exit  -i RECEPTOR           Input protein file with pdb format.  -l LIGAND [LIGAND ...]                        Ligand files to calculate binding energy.  -c CONFIG             Configue file, default: /opt/miniconda3/envs/test/lib/python3.10/site-packages/unigbsa-0.0.9.dev0-py3.10.egg/unigbsa/data/default.ini  -d LIGDIR             Floder contains many ligand files. file format: .mol or .sdf  -f PBSAFILE           gmx_MMPBSA input file. default=None  -o OUTFILE            Output file.  -nt THREAD            Set number of thread 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.csv10/08/2022 13:46:09 PM - INFO - Build protein topology.10/08/2022 13:46:10 PM - INFO - Build ligand topology: 1ceb_ligand1 molecule converted10/08/2022 13:46:13 PM - INFO - Running energy minimization: 1ceb_ligand10/08/2022 13:46:14 PM - INFO - Run the MMPB(GB)SA.10/08/2022 13:46:18 PM - INFO - Clean the results.================================================================================Results: Energy.csv Dec.csvFrames    mode    detal_G(kcal/mole)     1      gb              -20.4421```## 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.```Bashusage: unigbsa-scan [-h] [-i RECEPTOR] [-pd PROTDIR] [-l LIGAND [LIGAND ...]] [-ld LIGDIR] -e E -c PARASFILE [-o OUTDIR]                    [-nt THREAD] [--verbose]GBSA Calculation.optional arguments:  -h, --help            show this help message and exit  -i RECEPTOR           Input protein file with pdb format.  -pd PROTDIR           Floder contains many protein files. file format: .pdb  -l LIGAND [LIGAND ...]                        Ligand files to calculate binding energy.  -ld LIGDIR            Floder contains many ligand files. file format: .mol or .sdf  -e E                  Experiment data file.  -c PARASFILE          Parameters to scan  -o OUTDIR             Output directory.  -nt THREAD            Set number of thread 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.```Bashusage: unigbsa-pipeline [-h] -i RECEPTOR [-l LIGAND [LIGAND ...]] [-c CONFIG] [-d LIGDIR] [-f PBSAFILE] [-o OUTFILE] [-nt THREAD] [--decomp] [--verbose]GBSA Calculation.optional arguments:  -h, --help            show this help message and exit  -i RECEPTOR           Input protein file with pdb format.  -l LIGAND [LIGAND ...]                        Ligand files to calculate binding energy.  -c CONFIG             Configue file, default: default.ini  -d LIGDIR             Floder contains many ligand files. file format: .mol or .sdf  -f PBSAFILE           gmx_MMPBSA input file. default=None  -o OUTFILE            Output file.  -nt THREAD            Set number of thread to run this program.  --decomp              Decompose the free energy. default:False  --verbose             Keep all the files.```You can change the parameters for the MM/GB(PB)SA calculations by providing a configue 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 gromacsindex.ndxfile which contains two groups namedRECEPTORandLIGAND`.unigbsa-traj -husage: unigbsa-traj [-h] -i INP -p TOP -ndx NDX [-m {gb,pb,pb+gb,gb+pb}] [-t TRAJ] [-indi INDI] [-dec] [-D]Free energy calcaulated by PBSA 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 recepror and ligand group.  -m {gb,pb,pb+gb,gb+pb}                        Method to calculate: gb, pb, pb+gb. default:gb  -t TRAJ               A trajectory file contains many structure frames. File format: xtc, pdb, gro...  -indi INDI            External dielectric constant. detault: 1.0  -dec                  Decompose the energy. default:false  -D                    DEBUG model, keep all the files.### unigbsa-buildtop>Topology preparation for a protein receptor and ligand(s) using gromacs.Bashunigbsa-buildtop -husage: unigbsa-buildtop [-h] [-p PROTEIN] [-l LIGAND] [-pf PROTFORCE] [-lf {gaff,gaff2}] [-o OUTDIR] [-c] [-verbose]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 forcefiled: gaff or gaff2.  -o OUTDIR         A output directory.  -c                Combine the protein and ligand topology. Suppport for one protein and more ligands. default:True  -verbose          Keep the directory or not.### unigbsa-buildsys>Build a simulation box for a protein-ligand complex.```bashunigbsa-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]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 forcefiled: 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         A output directory.```### unigbsa-md>Run a MD simulation of a protein-ligand complex.```Bashunigbsa-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] [-nstep NSTEP] [-nframe NFRAME] [-verbose]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 forcefiled: 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         A output directory.  -nstep NSTEP      Simulation steps. default:2500  -nframe NFRAME    Number of frame to save for the xtc file. default:100  -verbose          Keep all the files in the simulation.```### unigbsa-pbc>Process PBC condition for a MD trajectory.```Bashunigbsa-pbc -husage: unigbsa-pbc [-h] -s TPR -f XTC [-o OUT] [-n NDX]Auto process PBC for gromacs MD trajector.optional arguments:  -h, --help  show this help message and exit  -s TPR      TPR file generated from gromacs or coordinate file.  -f XTC      Trajector file to process PBC.  -o OUT      Result file after processed PBC.  -n NDX      Index file contains the center and output group.```### More Examples* Perform a MM/GB(PB)SA calculation on a ligand file with a protein receptor withunigbsa-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 withunigbsa-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 trjectorywith ``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.```