Protein-ligand binding free energy calculations (Single Trajectory method) with CHARMMff files¶

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 -cp topol.top -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 gmx_MMPBSA MPI -O -i mmpbsa.in -cs com.tpr -ci index.ndx -cg 1 13 -ct com_traj.xtc -cp topol.top -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

gmx_MMPBSA_test -t 10

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

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Sample input file for PB 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-CHARMM",
startframe=1,
endframe=4,
# In gmx_MMPBSA v1.5.0 we have added a new PB radii set named charmm_radii. 
# This radii set should be used only with systems prepared with CHARMM force fields. 
# Uncomment the line below to use charmm_radii set
#PBRadii=7,
/
&pb
# radiopt=0 is recommended which means using radii from the prmtop file for both the PB calculation and for the NP
# calculation
istrng=0.15, fillratio=4.0, radiopt=0
/

See a detailed list of all the options in gmx_MMPBSA input file here as well as several examples

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 (1 13) are needed. The mmpbsa.in input file will contain all the parameters needed for the MM/PB(GB)SA calculation. A topology file is also needed (mandatory) in this case to generate the topology files in amber format with all the terms for CHARMM force field.

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.