Protein Titration Benchmark of CHARMM36, Amber99sb-ildn, Amber14sb, OPLS-AA/M, and Martini 2 Force Fields for Constant pH Molecular Dynamics in GROMACS.
- 1Computational Physics Laboratory, Tampere University, 33720Tampere, Finland.
- 2Theoretical Physics and Center for Biophysics, Saarland University, 66123Saarbrücken, Germany.
Abstract
Constant pH molecular dynamics (CpHMD) has emerged as a powerful method for simulating pH-dependent processes in proteins and other biomolecules. The original implementation of the PME-based CpHMD in the GROMACS software included the CHARMM36 and Martini 2 force fields for the treatment of the titratable amino acids in proteins. As requested by the user community, this work contains the parametrization of titratable residues for the Amber99sb-ildn, Amber14sb, and OPLS-AA/M force fields. In addition to carefully carrying out the parametrization process, the performance of the different force fields in the scope of CpHMD is evaluated by performing computational titrations for a set of benchmark proteins. The calculated pKa values obtained using all force fields yield an average root-mean-square error of about 1 pH unit in comparison to experimental pKa values, which is in line with previous CpHMD benchmarks. The presented work expands the applicability of the PME-based CpHMD method in GROMACS and guides the researchers aiming to perform accurate and efficient CpHMD simulations.
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BibTeX
@article{aho2026protein,
title = {{Protein Titration Benchmark of CHARMM36, Amber99sb-ildn, Amber14sb, OPLS-AA/M, and Martini 2 Force Fields for Constant pH Molecular Dynamics in GROMACS.}},
author = {Noora Aho},
journal = {Journal of chemical theory and computation},
year = {2026},
month = sep,
doi = {10.1021/acs.jctc.6c00678},
url = {https://europepmc.org/article/MED/42917451},
note = {CC BY},
}
RIS
TY - JOUR
TI - Protein Titration Benchmark of CHARMM36, Amber99sb-ildn, Amber14sb, OPLS-AA/M, and Martini 2 Force Fields for Constant pH Molecular Dynamics in GROMACS.
AU - Noora Aho
PY - 2026
DA - 2026/09/01
JO - Journal of chemical theory and computation
DO - 10.1021/acs.jctc.6c00678
UR - https://europepmc.org/article/MED/42917451
AB - Constant pH molecular dynamics (CpHMD) has emerged as a powerful method for simulating pH-dependent processes in proteins and other biomolecules. The original implementation of the PME-based CpHMD in the GROMACS software included the CHARMM36 and Martini 2 force fields for the treatment of the titratable amino acids in proteins. As requested by the user community, this work contains the parametrization of titratable residues for the Amber99sb-ildn, Amber14sb, and OPLS-AA/M force fields. In addition to carefully carrying out the parametrization process, the performance of the different force fields in the scope of CpHMD is evaluated by performing computational titrations for a set of benchmark proteins. The calculated pKa values obtained using all force fields yield an average root-mean-square error of about 1 pH unit in comparison to experimental pKa values, which is in line with previous CpHMD benchmarks. The presented work expands the applicability of the PME-based CpHMD method in GROMACS and guides the researchers aiming to perform accurate and efficient CpHMD simulations.
SN - 1549-9618
SN - 1549-9626
ER -