Force Field Limitations of All-Atom Continuous Constant pH Molecular Dynamics.

ABSTRACT: All-atom constant pH molecular dynamics simulations offer a powerful tool for understanding pH-mediated and proton-coupled biological processes. As the protonation equilibria of protein sidechains are shifted by electrostatic interactions and desolvation energies, pK _a values calculated from the constant pH simulations may be sensitive to the underlying protein force field and water model. Here we investigated the force field dependence of the all-atom particle mesh Ewald (PME) continuous constant pH (PME-CpHMD) simulations of a mini-protein BBL. The replica-exchange titration simulations based on the Amber ff19sb and ff14sb force fields with the respective water models showed significantly overestimated pK _a downshifts for a buried histidine (His166) an

SUBMITTER: Peeples CA 

PROVIDER: S-EPMC11398383 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature