Protein-ligand binding free energy calculations (Multiple Trajectory method)¶

Requirements¶

In this case, gmx_MMPBSA requires:

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

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 -ci index.ndx -cg 1 13 -ct com_traj.xtc -rs rec.pdb -ri rec_index.ndx -rg 1 -rt rec_traj.pdb -lm ligand.mol2 -ls lig.pdb -li lig_index.ndx -lg 2 -lt lig_traj.pdb -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ci index.ndx -cg 1 13\
       -ct com_traj.xtc -rs rec.pdb -ri rec_index.ndx -rg 1 -rt rec_traj.pdb \
       -lm ligand.mol2 -ls lig.pdb -li lig_index.ndx -lg 2 -lt lig_traj.pdb -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

gmx_MMPBSA_test -t 16

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

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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-MT",
startframe=5,
endframe=14,
forcefields="oldff/leaprc.ff99SB",leaprc.gaff"
/
&gb
igb=5, saltcon=0.150,
/

Considerations¶

In this case, a multiple trajectory (MT) approximation is followed, which means the receptor and ligand structures and trajectories are needed. For the complex, 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 (1 13) are needed. For the receptor, an MD Structure+mass(db) file (rec.pdb), an index file (rec_index.ndx), a trajectory file (rec_traj.pdb), and the receptor group number in the rec_index file (1) are needed. For the ligand, a ligand .mol2 file is needed for generating the ligand topology. Besides, an MD Structure+mass(db) file (lig.pdb), an index file (lig_index.ndx), a trajectory file (lig_traj.pdb), and ligand group number in the lig_index file (2) are needed. 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.