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Protein-protein binding free energy calculations

Info

This example can be found in the examples/Protein_ligand directory in the repository folder. If you didn't use gmx_MMPBSA_test before, use downgit to download the specific folder from xBFreE GitHub repository.

Requirements

Depending on the MD engine and force field used, xBFreE requires specific files:

Input File required 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 Group numbers in the index files
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
Input File required 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 pdb Structure file containing the system coordinates
Receptor and ligand masks range The "mask" selection expressions start with ":". Residues can be selected by numbers (given as ranges separated by a dash) e.g. :1-30 :31-39
A trajectory file nc pdb mdcrd Final AMBER MD trajectory, fitted and with no pbc.
A topology file parm7 prmtop AMBER topology file

This is based on the standard output of CHARMM-GUI online server

Input File required 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 pdb Structure file containing the system coordinates
Receptor and ligand masks range The "mask" selection expressions start with ":". Residues can be selected by numbers (given as ranges separated by a dash) e.g. :1-30 :31-39
A trajectory file pdb dcd Final NAMD MD trajectory, fitted and with no pbc.
A topology file parm7 prmtop Topology file in amber format

This is based on the standard output of CHARMM-GUI online server

Input File required 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 pdb Structure file containing the system coordinates
Receptor and ligand masks range The "mask" selection expressions start with ":". Residues can be selected by numbers (given as ranges separated by a dash) e.g. :1-30 :31-39
A trajectory file pdb dcd Final NAMD MD trajectory, fitted and with no pbc.
A topology file psf Topology file in psf format

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

See a detailed list of all the flags in xBFreE command line here

Command-line

That being said, once you are in the folder containing all files, the command-line will be as follows:

xbfree gmx_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.pdb -ci index.ndx -cg 1 18 -cp topol.top -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 xbfree gmx_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.pdb -ci index.ndx -cg 1 18 -cp topol.top -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

xbfree amber_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.pdb -cg :1-58 :59 -cp com.parm7 -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 xbfree amber_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.pdb -cg :1-58 :59 -cp com.parm7 -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

xbfree namd_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.pdb -cg :1-58 :59 -cp com.parm7 -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 xbfree namd_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.pdb -cg :1-58 :59 -cp com.parm7 -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

xbfree namd_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.dcd -cg :1-58 :59 -cp com.psf -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 xbfree namd_MMPBSA -O -i mmpbsa.in -cs com.pdb -ct com_traj.dcd -cg :1-58 :59 -cp com.psf -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 GB calculation
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Sample input file for GB calculation
This input file is meant to show only that xBFreE 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",
startframe=1,
endframe=5,
/
&gb
igb=2, saltcon=0.150,
/

Keep in mind

See a detailed list of all the options in xBFreE input file here as well as several examples. These examples are meant only to show that xBFreE 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, a trajectory file, an index file (for those using GROMACS) and both the receptor and ligand group numbers or masks are needed. The mmpbsa.in input file will contain all the parameters needed for the MM/PB(GB)SA calculation. In this case, 5 frames are going to be used when performing the MM/PB(GB)SA calculation with the igb2 (GB-OBC1) 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.

Note

Once the calculation is done, the results can be analyzed in xBFreE-Analyzer (if -nogui flag was not used in the command-line). Please, check the xBFreE-Analyzer section for more information

2023-10-26 2023-03-26