Binding free energy calculation with linear PB (NLPBE)¶

Info

in gmx_MMPBSA v1.5.0!!!

This example can be found in the examples/NonLinear_PB_solver 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	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`	Receptor and ligand group numbers in the index file
A trajectory file	`xtc` `pdb` `trr`	Final GROMACS MD trajectory, fitted and with no pbc.
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

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:

SerialWith MPI

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

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

Sample input file for NLPB calculation
Sample input file for NLPB
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="NonLinear_PB",
startframe=1,
endframe=10,
forcefields="leaprc.protein.ff14SB",
/
&pb
npbopt=1,
indi=1.0, istrng=0.15,                                                     
radiopt=0,                                           
eneopt=1, cutnb=8.0,
/
# check these threads 
# http://archive.ambermd.org/201203/0191.html
# http://archive.ambermd.org/201610/0114.html
# for more info on NLPB

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 amber format topologies 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. The mmpbsa.in input file will contain all the parameters needed for the MM/PB(GB)SA calculation. In this case, 6 frames are going to be used when performing the MM/PB(GB)SA calculation with the Non-Linear PB solver (npbopt=1). The dielectric constant (indi) is set = 1.

Warning

When running a NLPB solver, eneopt is set = 1. That way, the total electrostatic energy and forces will be computed with the particle-particle particle-mesh (P3M) procedure outlined in Lu and Luo. In doing so, energy term EPB in the output file is set to zero, while EEL term includes both the reaction field energy (EPB) and the Coulombic energy (EEL). The van der Waals energy is computed along with the particle-particle portion of the Coulombic energy. This option requires a nonzero cutnb (in this case, cutnb=8.0) and bcopt = 5 (default option).

It's noteworthy mentioning that ΔGGAS and ΔGSOLV as reported are no longer properly decomposed. Since EPB and EEL are combined into the "gas phase" term, the gas and solvation terms can't be separated. Nevertheless, the total ΔTOTAL should be perfectly fine, since everything is sum up together in the end.

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