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s_mmpbsa

s_mmpbsa: Supernova's tool of binding free energy calculation for Gromacs trajectory, using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method.

The s_mmpbsa program follows LGPL license, and can be freely used for academic purposes.

Documentation

The detailed documentations could be found here. https://s-mmpbsa.readthedocs.io/en/latest/

Introduction

MM-PBSA method is the most popular method to rapidly calculate binding free energy, especially for biological systems. However, as a widely-used MD program, Gromacs has not officially support MM-PBSA calculation. Although there have been numerous programs that can calculate binding free energy with GROMACS trajectory, most of them have some limitations at different aspects, for example: (1) Difficult to use and install (2) Lack of support for new version of Gromacs (3) Too slow (4) Not cross-platform. Instead, s_mmpbsa provides a convenient interface (like Multiwfn) to calculate binding free energy for GROMACS trajectory.

Features of s_mmpbsa

  • Open source and freely available.
  • Less need for running environment preparation, only needs Gromacs program when running on linux system, and Python environment for plotting.
  • In contrast to other programs, s_mmpbsa is developed with Rust.
  • Interactive operation, no need to write parameter files. Also, user can write shell script to invoke s_mmpbsa for batch use.
  • Considers electric screening effect, as "J. Chem. Inf. Model. 2021, 61, 2454".
  • Considers conformational entropy, as "J. Chem. Phys. 2017, 146, 124124".
  • Could store analyzation results for further reproducable analyzation.

Main function

  • Binding energy calculation from MD simulation.
  • Alanine scanning of protein-ligand complex.

Requirement

Basic requirements

  • Gromacs: The gromacs program is needed on Linux.
  • APBS: (Optional) The PBSA kernel is already built-in, but it is also supported to use other version of APBS programs.
  • PyMOL: an optional software to plot the B-factor colored structure.

Usage

Although s_mmpbsa supports fixing PBC conditions to trajectory .MMPBSA_[name].xtc, it is still recommended to comfirm that the trajectory has been correct, using visualization software such as VMD:

vmd `.MMPBSA_[name]_struct.gro` `.MMPBSA_[name].xtc`

MD Binding energy calculation:

# Firstly, add s_mmpbsa folder to $PATH.
# Start s_mmpbsa, and input as follow (support # comments, but not recommended and usually no need to input with comments)
s_mmpbsa -f md_pbc.xtc -s md.tpr -n index.ndx
0 # go to next step (Trajectory Parameters)
1 # select receptor group
[protein group number]
2 # select ligand group
[ligand group number]
0 # go to next step (MM-PBSA Parameters)
# Other options usually no need to change. The PB and SA parameters could be modified by 8 and 9
0 # go to next step (start calculation)
[return] # use default name "system" or input specific name
# Wait for calculation finish
-1 # write pdb file with residue-wised INVERSED binding energy filled in B-factor column
# input the time point
1 # view summary
2 # output energy by time
3 # output energy by residue
# input the time point (default average)
# input the residues range (default all)
0 # exit s_mmpbsa program

Alanine scanning:

# At MM-PBSA Parameters page
2 # Do alanine scanning
1 # Select mutation residues by layers (ACS Catal. 2024, 14, 15, 11447–11456)
0 # Start calculation
...

The results will contain energy terms of both wild type and mutants.

Use Analyzation mode:

# Firstly, add s_mmpbsa folder to $PATH.
# Start s_mmpbsa, and input as follow (support # comments, but not recommended and usually no need to input with comments)
s_mmpbsa -a MMPBSA_[name]_WT.sm # analyzation mode
... (same as above)

The data was generated with .csv format and plotted as figures; The pdb files with inversed binding energy filled in B-factors column are drawn as png figures by PyMOL (if usable).

Download

Release file: https://github.com/supernova4869/s_mmpbsa/releases/latest, where "s_mmpbsa.exe" and "s_mmpbsa" are s_mmpbsa executable files on Windows and Linux operation systems, respectively.

Citation

The s_mmpbsa program should be properly cited if the work will be published.

Currently, s_mmpbsa is still in-develop. If you want to utilize s_mmpbsa in your work, please cite the program as following:

Jiaxing Zhang, s_mmpbsa, Version [your version], https://github.com/supernova4869/s_mmpbsa (accessed on yy-mm-dd)

After the detailed paper about s_mmpbsa is published (if fortunately), please cite the corresponding paper instead of the web page here.

About developer

Dr. Jiaxing Zhang (Contact: zhangjiaxing7137@tju.edu.cn, Tianjin University)

If you encountered any difficulty while using s_mmpbsa, or you found any bugs, or you have any suggestion on improving s_mmpbsa, please E-mail me or join my QQ group 864191465 to describe.

New Folder (?

  • Support built-in PBSA solvers

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Supernova's MM-PBSA binding free energy calculation tool.

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