gmx_MMPBSA in a nutshell¶

gmx_MMPBSA makes the capabilities of MMPBSA.py available to GROMACS users. It also supports additional functionality, including MM/PB(GB)SA calculations with a user-defined internal dielectric constant and interaction entropy and C2 entropy calculations. The gmx_MMPBSA_ana graphical application provides interactive result visualization and can export high-quality figures.

Types of calculations you can do¶

There are many options available in gmx_MMPBSA. These are some calculations you can perform with gmx_MMPBSA:

• Standard binding free energies with PB, GB, or 3D-RISM solvent models. These calculations can use one, two, or three trajectories. The complex trajectory is always required. If the receptor and/or ligand trajectories are not specified, they are extracted from the complex trajectory. PB and GB calculations are performed with sander, while 3D-RISM calculations are also launched through the AmberTools sander backend; gmx_MMPBSA distributes frame work across MPI ranks and collects rank-specific RISM output.
• Stability calculations with any solvent model (i.e PB, GB or 3D-RISM).
• Alanine scanning with PB or GB implicit-solvent models. The trajectories are mutated to match the mutant topologies, and the requested calculations are performed for both the original and mutant systems. A run can mutate one residue or several residues together in one composite mutant; it does not independently scan each selected residue. The target residues must be mutated to alanine or glycine. Unless mutant_only is set to 1, the output also reports the differences caused by the mutation.
• Entropy corrections. An entropy term can be added to the free energies calculated above using the normal mode, interaction entropy or C2 approximations. Quasi-harmonic data from historical result files can still be inspected in this final compatibility release; all QH support will be removed afterward. Calculations will be performed for the normal and mutated systems (alanine scanning) as requested. Normal mode calculations are done with the mmpbsa_py_nabnmode program included with AmberTools.
• Decomposition schemes. The energy terms will be decomposed according to the decomposition scheme (per-residue or per-wise) outlined in the idecomp variable description. This should work with all the above, though entropy terms cannot be decomposed.
• QM/MMGBSA. This is a binding free energy (or stability calculation) using the Generalized Born solvent model allowing you to treat part of your system with a quantum mechanical Hamiltonian.
• Support for Membrane Proteins. Calculate the MMPBSA binding free energy for a ligand bound to a protein that is embedded into a membrane. In this case, the membrane is implemented as a slab-like region with a uniform or heterogeneous dielectric constant depth profile.
• Native AMBER calculations through amber_MMPBSA, using AMBER topology, coordinate, trajectory, and mask files. Supported ST and MT methods, plus native-AMBER restrictions and experimental paths, are documented in the dedicated guide.

A technical view of gmx_MMPBSA¶

gmx_MMPBSA is a Python package that contains four applications:

• gmx_MMPBSA is the main application and carries out the calculations described above
• amber_MMPBSA runs the supported native-AMBER workflows without requiring GROMACS input files
• gmx_MMPBSA_ana provides an intuitive way to analyze the data from gmx_MMPBSA calculations and save high-quality pictures
• gmx_MMPBSA_test tests whether the installation was successful by running one or more available examples in gmx_MMPBSA.