Force fields matter in DNA pol $$ \eta $$ mechanistic analysis.

ABSTRACT: DNA polymerase η$$ \eta $$ is of major interest due to debates regarding the role of a third non-canonical magnesium ion in catalysis. By examining molecular simulations motivated by this mechanistic question and the role of the S113A mutation, we investigate how modern classical force fields compare for treating protein-DNA complexes and divalent metal ions in enzyme active sites. We find that while the CHARMM36m protein force field is robust, the nucleic acid components are unstable and too flexible, leading to the active site conformation in the reactant state not being well maintained. The addition of the third magnesium ion reduces but does not eliminate these issues, and the observed trends do not match experimental data and the magnesium ions bind too strongly. The AMBER19 force fie

SUBMITTER: Osadchey R 

PROVIDER: S-EPMC12723750 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature