Alanine scanning¶

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 -ct com_traj.xtc -ci index.ndx -cg 3 4 -cp topol.top -cr com.pdb -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 -cr com.pdb -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

gmx_MMPBSA_test -t 12

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

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Sample input file for Alanine scanning
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="Alanine_Scanning",
startframe=1,
endframe=10,
forcefields="leaprc.protein.ff14SB",
PBRadii=4,
/
&gb
igb=8, saltcon=0.150,
/
&alanine_scanning
mutant='ALA', mutant_res='R:23', cas_intdiel=1
/

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, 10 frames are going to be used when performing the MM/PB(GB)SA calculation with the igb8 (GB-Neck2) model and a salt concentration = 0.15M. Of note, mbondi3 radii (PBRadii=4) will be used as recommended for GB-Neck2 solvation model. Also, The dielectric constant (intdiel) will be modified depending on the nature of the residue to be mutated as cas_intdiel=1. In this case, the residue R/23 is a Tyrosine which means intdiel = 3 will be used. Note also that we used a reference structure to ensure that the selection process for the residue to be mutated is successful (see below).

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.

How to define properly which residue is going to be mutated?¶

The generated PDB files must keep the original numbering, so selection based on residue number is reliable. However, the chain id can vary depending on several factors. If you use the reference structure (-cr flag), then you don't have to worry about any changes. The selection will be based on this structure.

On the other hand, if this reference structure is omitted, then it will depend on:

• GROMACS version

  We have noticed that in GROMACS 20xx.x versions, trjconv can omit the chain IDs.

• The option assign_chainID

  This option defines when chain IDs are assigned. Please see this variable in &general namelist variables section