Ab initio study of the physical nature of interactions between enzyme active site fragments invacuo

Abstract

A recently developed direct version of variation–perturbation decomposition of intermolecular interaction energy into electrostatic, exchange, delocalization and correlation components has been used to explore the physical nature of interactions between key fragments of several enzyme active sites and corresponding reactants or inhibitors in acuo. Despite neglecting solvent effects our results correlate reasonably with available experimental data and indicate the dominant electrostatic nature of inhibitory effects of PheP derivatives in leucine aminopeptidase and pK_a shifts resulting from amino acid substitutions in mutated subtilisins. The range of applicability of the electrostatic approximation has been examined for the chorismate mutase enzyme.