How xBFreE (MMPBSA) works¶
xBFreE implements all the features in gmx_MMPBSA with support for GROMACS, AMBER, NAMD, and CHARMM. Hereafter, we refer to xBFreE (MMPBSA) as the module used to perform binding free energy calculations employing PB and other implicit solvent-based approaches.
General workflow in xBFreE (MMPBSA)¶
The calculations can be divided into 2 parts as shown in figure 1. In the first part, Preparation, the topologies and trajectories are generated, among other elements depending on the calculations and MD program, such as the mutants for the alanine/glycine scanning or the list of interacting residues during decomposition analysis. In the second part, Calculation, the binding free energies and/or entropies are estimated using the selected models.
For gmx_MMPBSA users
Note that the analysis of the results is now outside the xBFreE workflow. This is because we have separated the xBFreE-Analyzer (formerly gmx_MMPBSA_ana) analysis tool as an independent module. See the xBFreE-Analyzer documentation for more information.
flowchart TD
subgraph preparation [Preparation]
A{{Complex}} -->|ST or MT| D
A -->|ST or MT| E
B{{Receptor}} -->|MT| D
B -->|MT| E
C{{Ligand}} -->|MT| D
C -->|MT| E
D[Topology] --> N[Molecule Selection]
N -->|Convert| I[Amber Topology]
E[Trajectory] --> F[Clean up]
F --> G[Fixed Trajectory]
end
G --> H
I --> H
subgraph calculation [Calculation]
H[Check Topologgy consistency] --> J[Create Input for external programs]
J --> K[Call external programs to calculate Energy and Entropy]
K --> L[Calculate statistics]
end
L --> M[Print final results]Figure 1. xBFreE (MMPBSA) general workflow
Required input files¶
Currently, only AMBER and CHARMM force fields are officially supported. Depending on the MD program, one or several different files are required.
| MD Program\Flags | -cp (Topology) | -cs (MD Structure) | -ct (Trajectory) | -cg (Groups) | -ci (Index) | -cr (Reference structure) |
|---|---|---|---|---|---|---|
| GROMACS | *.top | *.tpr, *.pdb | *.xtc, *.trr | group numbers or names | *.ndx | *.pdb |
| AMBER | *.prmtop, *.parm7 | *.pdb1 | *.nc, *.crd, *.mdcrd | amber masks | ||
| NAMD | *.psf, *.parm7 | *.pdb1 | *.dcd | amber masks | ||
| CHARMM | *.psf | *.pdb1 | *.dcd | amber masks |
For gmx_MMPBSA users!
Note that the generation of the Amber topology from structures is no longer supported. Now only the topology is required, no matter which force field or MD program was used. This also removes some confusing flags and variables, for example, the -lm flag and the forcefields variable.
Topology preparation¶
In this section, we will go in detail about each file and what they are used for.
flowchart TD
subgraph input [Input]
a1{{"GROMACS\n(*.top)"}}
b1{{"AMBER\n(*.prmtop, *.parm7)"}}
c1{{"CHARMM\n(*.psf)"}}
d1{{NAMD}} -->|"AMBER FF\n (*.parm7)"| b1
d1{{NAMD}} -->|"CHARMM FF\n (*.psf)"| c1
end
subgraph topology [Topology Preparation]
a1 --> a2[Generate Custom Index]
b1 --> c2[Get amber mask]
c1 --> c2
a2 --> common
c2 --> common
subgraph common [Common steps]
b2[Generate pdb files]
g2[Check PDB consistency]
h2[Clean up the topology]
i2[Assign PBRadii]
j2[Convert topology]
k2[Save topology]
b2 --> g2 --> h2 --> i2 --> j2 --> k2
end
end
k2 --> a4[Amber Topolgy]