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

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 gmxMMPBSA, a new tool to perform end-state free energy calculations from GROMACS molecular dynamics trajectories. gmxMMPBSA 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 gmxMMPBSA. Two additional tools-gmxMMPBSAₜest and gmxMMPBSAₐna-have been integrated within gmxMMPBSA to improve its usability. Multiple illustrating examples can be accessed through gmxMMPBSAₜest, while gmxMMPBSAₐna provides fast, easy, and efficient access to different graphics plotted from gmxMMPBSA output files. The latest version (v1. 4. 3, 26/05/2021) is available free of charge (documentation, test files, and tutorials included) at https: //github. com/Valdes-Tresanco-MS/gmxMMPBSA.