Expanding gmx_MMPBSA capabilities for end-state binding free energy calculations with GROMACS and AMBER
Abstract
gmx_MMPBSA is an end-to-end tool for performing end-state binding free energy calculations. Here, we present advances in the gmx_MMPBSA suite that simplify preparation, expand the calculation options, and improve the analysis of results. The new features include the GBNSR6 and nonlinear PB models, second-order cumulant (C2) entropy estimation, inclusion of explicit structural waters, and multiple alanine/glycine mutations. We also introduce amber_MMPBSA, a new entry point that accepts native AMBER input files and extends the calculation and analysis capabilities of gmx_MMPBSA to AMBER users. The redesigned graphical analyzer, gmx_MMPBSA_ana, and modernized Python API facilitate exploration of large datasets and comparisons across multiple systems. We illustrate the new gmx_MMPBSA capabilities using a diverse set of biomolecular complexes (protein-protein, protein-RNA, protein-small molecule, DNA-small molecule) and show how the calculated binding energies vary across systems depending on the methodological choices. The source code is available at https://github.com/Valdes-Tresanco-MS/gmx_MMPBSA.
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BibTeX
@misc{valdestresanco2026expanding,
title = {{Expanding gmx_MMPBSA capabilities for end-state binding free energy calculations with GROMACS and AMBER}},
author = {M. E. Valdes-Tresanco and M. S. Valdes-Tresanco and G. Romero-Hernandez and P. A. Valiente and E. Moreno},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.24.761505},
url = {https://www.biorxiv.org/content/10.64898/2026.10.24.761505v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Expanding gmx_MMPBSA capabilities for end-state binding free energy calculations with GROMACS and AMBER
AU - M. E. Valdes-Tresanco
AU - M. S. Valdes-Tresanco
AU - G. Romero-Hernandez
AU - P. A. Valiente
AU - E. Moreno
PY - 2026
DA - 2026/10/24
PB - bioRxiv
DO - 10.64898/2026.10.24.761505
UR - https://www.biorxiv.org/content/10.64898/2026.10.24.761505v1
AB - gmx_MMPBSA is an end-to-end tool for performing end-state binding free energy calculations. Here, we present advances in the gmx_MMPBSA suite that simplify preparation, expand the calculation options, and improve the analysis of results. The new features include the GBNSR6 and nonlinear PB models, second-order cumulant (C2) entropy estimation, inclusion of explicit structural waters, and multiple alanine/glycine mutations. We also introduce amber_MMPBSA, a new entry point that accepts native AMBER input files and extends the calculation and analysis capabilities of gmx_MMPBSA to AMBER users. The redesigned graphical analyzer, gmx_MMPBSA_ana, and modernized Python API facilitate exploration of large datasets and comparisons across multiple systems. We illustrate the new gmx_MMPBSA capabilities using a diverse set of biomolecular complexes (protein-protein, protein-RNA, protein-small molecule, DNA-small molecule) and show how the calculated binding energies vary across systems depending on the methodological choices. The source code is available at https://github.com/Valdes-Tresanco-MS/gmx_MMPBSA.
ER -