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Protein-ligand binding free energy calculations (Single Trajectory method)

Info

This example can be found in the examples/Protein_ligand/ST directory in the repository folder. If you didn't use gmx_MMPBSA_test before, use downgit to download the specific folder from gmx_MMPBSA GitHub repository.

Requirements

In this case, gmx_MMPBSA requires:

Input File required Required Type Description
Input parameters file in Input file containing all the specifications regarding the type of calculation that is going to be performed
The MD Structure+mass(db) file tpr pdb Structure file containing the system coordinates
An index file ndx File containing the receptor and ligand in separated groups
Receptor and ligand group integers Group numbers in the index files
A trajectory file xtc pdb trr Final GROMACS MD trajectory, fitted and with no pbc.
Ligand parameters file mol2 The Antechamber output mol2 file of ligand parametrization
A topology file top GROMACS topology file (The * .itp files defined in the topology must be in the same folder
A Reference Structure file pdb Complex reference structure file (without hydrogens) with the desired assignment of chain ID and residue numbers

-> Must be defined -- -> Optional, but recommended -- -> Optional

Remember

When a topology file is defined, the ligand mol2 file is not needed. The ligand mol2 file only required when
gmx_MMPBSA build the amber topology from a structure. The ligand mol2 file must be the Antechamber output.

See a detailed list of all the flags in gmx_MMPBSA command line here

Command-line

That being said, once you are in the folder containing all files, the command-line will be as follows:

gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ct com_traj.xtc -ci index.ndx -cg 3 4 -cp topol.top -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ct com_traj.xtc -ci index.ndx -cg 3 4 -cp topol.top -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

gmx_MMPBSA_test -t 3

where the mmpbsa.in input file, is a text file containing the following lines:

Sample input file for GB calculation
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Sample input file for GB calculation
This input file is meant to show only that gmx_MMPBSA works. Althought,
we tried to used the input files as recommended in the Amber manual,
some parameters have been changed to perform more expensive calculations
in a reasonable amount of time. Feel free to change the parameters 
according to what is better for your system.

&general
sys_name="Prot-Lig-ST",
startframe=1,
endframe=10,
/
&gb
igb=5, saltcon=0.150,
/

Keep in mind

See a detailed list of all the options in gmx_MMPBSA input file here as well as several examples. These examples are meant only to show that gmx_MMPBSA works. It is recommended to go over these variables, even the ones that are not included in this input file but are available for the calculation that it's performed and see the values they can take (check the input file section). This will allow you to tackle a number of potential problems or simply use fancier approximations in your calculations.

Considerations

In this case, a single trajectory (ST) approximation is followed, which means the receptor and ligand structures and trajectories will be obtained from that of the complex. To do so, an MD Structure+mass(db) file (com.tpr), an index file (index.ndx), a trajectory file (com_traj.xtc), and both the receptor and ligand group numbers in the index file (3 4) are needed. A ligand .mol2 file is also needed for generating the ligand topology. The mmpbsa.in input file will contain all the parameters needed for the MM/PB(GB)SA calculation. In this case, 10 frames are going to be used when performing the MM/PB(GB)SA calculation with the igb5 (GB-OBC2) model and a salt concentration = 0.15M.

A plain text output file with all the statistics (default: FINAL_RESULTS_MMPBSA.dat) and a CSV-format output file containing all energy terms for every frame in every calculation will be saved. The file name in '-eo' flag will be forced to end in [.csv] (FINAL_RESULTS_MMPBSA.csv in this case). This file is only written when specified on the command-line.

Note

Once the calculation is done, the results can be analyzed in gmx_MMPBSA_ana (if -nogui flag was not used in the command-line). Please, check the gmx_MMPBSA_ana section for more information

Last update: 2023-06-24
Created: 2023-06-24