gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS

Abstract

Molecular mechanics/Poisson–Boltzmann (Generalized-Born) surface area is one of the most popular methods to estimate binding free energies. This method has been proven to balance accuracy and computational efficiency, especially when dealing with large systems. As a result of its popularity, several programs have been developed for performing MM/PB­(GB)­SA calculations within the GROMACS community. These programs, however, present several limitations. Here we present gmx_MMPBSA, a new tool to perform end-state free energy calculations from GROMACS molecular dynamics trajectories. gmx_MMPBSA provides the user with several options, including binding free energy calculations with different solvation models (PB, GB, or 3D-RISM), stability calculations, computational alanine scanning, entropy corrections, and binding free energy decomposition. Noteworthy, several promising methodologies to calculate relative binding free energies such as alanine scanning with variable dielectric constant and interaction entropy have also been implemented in gmx_MMPBSA. Two additional toolsgmx_MMPBSA_test and gmx_MMPBSA_anahave been integrated within gmx_MMPBSA to improve its usability. Multiple illustrating examples can be accessed through gmx_MMPBSA_test, while gmx_MMPBSA_ana provides fast, easy, and efficient access to different graphics plotted from gmx_MMPBSA output files. The latest version (v1.4.3, 26/05/2021) is available free of charge (documentation, test files, and tutorials included) at .

Molecular basis for redox control by the human cystine/glutamate antiporter system xc−

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Discovery of small molecular inhibitors for interleukin-33/ST2 protein–protein interaction: a virtual screening, molecular dynamics simulations and binding free energy calculations

“…The gmx_MMPBSA package was used for calculations based on the single trajectory of GROMACS with CHARMM-27 forcefield [ 53 ]. This tool allows free energy calculations using MM/PBSA or GBSA (Molecular Mechanics/ Poisson-Boltzmann or Generalized Born Surface Area) methods.…”

In Silico Analysis of Metabolites from Peruvian Native Plants as Potential Therapeutics against Alzheimer’s Disease

“…The molecular mechanics generalized born surface area (MM/GBSA) was used to determine the binding free energy of receptor–ligand using gmx MMPBSA v1.4.1 [ 112 ] tool based on MMPBSA.py [ 113 ], from AmberTools20 suite. In general, this estimation calculates the free energy difference between the bound and unbound form of the receptor as the following equation: ΔG bind = G complex − G protein − G ligand where ΔG bind is the binding free energy and G complex (free energy of complex), G protein (free energy of protein), and G ligand (free energy ligand).…”

“…The molecular mechanics generalized born surface area (MM/GBSA) was used to determine the binding free energy of receptor-ligand using gmx MMPBSA v1.4.1 [112] tool based on MMPBSA.py [113], from AmberTools20 suite. In general, this estimation calculates the free energy difference between the bound and unbound form of the receptor as the following equation:…”