Electronic Continuum Model for Molecular Dynamics Simulations of Biological Molecules

摘要

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 a vacuum. As a result, the electrostatic interactions between ionized groups are exaggerated in molecular simulations by a factor of about 2. The model discussed here, MDEC (Molecular Dynamics in Electronic Continuum) provides a theoretical framework for modification of the standard nonpolarizable 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 bridge in cytochrome c oxidase, we compared the standard nonpolarizable MD simulations with MDEC simulations and demonstrated that the 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 nonpolarizable force fields simulations.