Electronic continuum model for molecular dynamics simulations of biological molecules.

Abstract

Electronic polarizability is an important factor in molecular interactions. In the conventional force fields such as AMBER or CHARMM, however, there is inconsistency in how the effect of electronic dielectric screening of Coulombic interactions, inherent for the condensed phase media, is treated. Namely, the screening appears to be accounted for via effective charges only for neutral moieties, whereas the charged residues are treated as if they were in vacuum. As a result, the electrostatic interactions between ionized groups are exaggerated in molecular simulations by the factor of about 2. The discussed here MDEC (Molecular Dynamics in Electronic Continuum) model provides a theoretical framework for modification of the standard non-polarizable force fields to make them consistent with the idea of uniform electronic screening of partial atomic charges. The present theory states that the charges of ionized groups and ions should be scaled; i.e. reduced by a factor of about 0.7. In several examples, including the interaction between Na (+) ions, which is of interest for ion-channel simulations, and the dynamics of an important salt-bride in Cytochrome c Oxidase, we compared the standard non-polarizable MD simulations with MDEC simulations, and demonstrated that MDEC charge scaling procedure results in more accurate interactions. The inclusion of electronic screening for charged moieties is shown to result in significant changes in protein dynamics and can give rise to new qualitative results compared with the traditional non-polarizable force fields simulations.