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Running MMPBSA calculations

Before any calculations

xBFreE requires minimum processing on the input structure and trajectory files. Before running any MMPBSA calculation, please make sure:

The structure defined in -cs, -rs, or -ls options is consistent

Visualize the structure contained in the structure input file given in the -cs, -rs, or -ls options and make sure it is consistent (as shown in Figure 1, right panel). If the structure is "broken" (as shown in Figure 1, left panel) this could generate inconsistent results.

The following procedure is executed with GROMACS. A similar processing can be performed with other softwares as well.

Generate the structure from tpr file:

gmx editconf -f md.tpr -o md.pdb

overview
Figure 1. Vizualization of two different input structures files. Left: "Broken" structure; Right: Centered structure

The trajectory defined in -ct, -rt, or -lt doesn't contain PBC

Visualize the trajectory given in the -ct, -rt, or -lt options and make sure the PBC has been removed (as shown in Figure 2, right panel). On the other hand, if the trajectory has not been fitted (as shown in Figure 2, left panel) this could generate inconsistent results.

The following procedure is executed with GROMACS. A similar processing can be performed with other softwares as well.

Steps:

  1. Generate a group that contains both molecules

    gmx make_ndx -n index.ndx

>1 | 12

>q

    Assuming 1 is the receptor and 12 is the ligand. This creates a new group (number 20 in this example)

  2. remove the PBC

    gmx trjconv -s md.tpr -f md.xtc -o md_noPBC.xtc -pbc mol -center -n -ur compact
center: 20 (created group)
output: 0

  3. remove the rotation and translation with respect to the reference structure (optional)

    gmx trjconv -s md.tpr -f md_noPBC.xtc -o md_fit.xtc -n -fit rot+trans
fit: 20 (created group)
output: 0

  4. Visualization

    Make sure that the trajectory is consistent (as shown in Figure 2, right panel)

  5. If the process is not succesful, consider using other options like -pbc nojump (as suggested here)

overview
Figure 2. Vizualization of two different input trajectory files. Left: Trajectory with PBC; Right: Trajectory centered, fitted and with PBC removed.

Running MMPBSA calculations

Tip

We currently recommend the use of MPI since the computation time decreases considerably.

xBFreE uses the MPI only to perform the calculations, the rest of the process (i.e, Generation/conversion of Amber topologies, mutation, division of the trajectories, etc.) occurs in a single thread (See Figure 3 for better reference). This means that it is not necessary to install any program (AmberTools or GROMACS) with MPI, which can be used in any circumstance, and the time required to process the data prior to the calculation depends on the system and will be the same for both versions (Serial and MPI).

Remember

Make sure that you have OpenMPI available in your computer

A usage example is shown below:

mpirun -np 2 xbfree gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ci index.ndx -cg 1 13 -ct com_traj.xtc

#!/bin/sh
#PBS -N nmode
#PBS -o nmode.out
#PBS -e nmode.err
#PBS -m abe
#PBS -M email@domain.edu
#PBS -q brute
#PBS -l nodes=1:surg:ppn=3
#PBS -l pmem=1450mb or > 5gb for nmode calculation

cd $PBS_O_WORKDIR

mpirun -np 3 xbfree gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ci index.ndx -cg 1 13 -ct com_traj.xtc > progress.log

Danger

Unfortunately, when running xbfree gmx_MMPBSA with MPI, GROMACS's gmx_mpi can't be used. This is probably because of gmx_mpi conflicts with mpirun. In any case, this is not a problem since gmx works correctly and gmx_mpi only parallels mdrun, the rest of the GROMACS tools work in a single thread. See this issue to see the output.

Warning

The PB/3D-RIMS/NMODE calculations require a considerable amount of RAM. Consider that the total amount of RAM will be:

RAMtotal = RAM1_frame * NUM of Threads

If the RAM of the system is consumed, it can cause crashes, instability or system shutdown!

This version is installed via pip as described above. AMBERHOME variable must be set, or it will quit with an error. An example command-line call is shown below:

xbfree gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ci index.ndx -cg 1 13 -ct com_traj.xtc

You can found test files on GitHub

drawing

Figure 3. MPI benchmark description from MMPBSA.py paper. MMPBSA.py scaling comparison for MM-PBSA and MM-GBSA calculations on 200 frames of a 5910-atom complex. Times shown are the times required for the calculation to finish. Note that MM-GBSA calculations are ∼5 times faster than MM-PBSA calculations. All calculations were performed on NICS Keeneland (2 Intel Westmere 6-core CPUs per node, QDR infiniband interconnect)

2023-07-14 2023-05-27