Electronic Polarization Is Essential for the Stabilization and Dynamics of Buried Ion Pairs in Staphylococcal Nuclease Mutants.

ABSTRACT: Buried charged residues play important roles in the modulation of protein stabilities and conformational dynamics and make crucial contributions to protein functions. Considering the generally nonpolar nature of protein interior, a key question concerns the contribution of electronic polarization to the stabilization and properties of buried charges. We answer this question by conducting free energy simulations using the latest polarizable CHARMM force field based on Drude oscillators for a series of Staphylococcal nuclease mutants that involve a buried Glu-Lys pair in different titration states and orientations. While a nonpolarizable model suggests that the ionized form of the buried Glu-Lys pair is more than 40 kcal/mol less stable than the charge-neutral form, the two titration

SUBMITTER: Deng J 

PROVIDER: S-EPMC9616648 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature