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

A recently developed direct version of variation-perturbation decomposition of intermolecular interaction energy into electrostatic, exchange, delocal ization and correlation components has been used to explore the physical na ture of interactions between key fragments of several enzyme active sites a nd corresponding reactants or inhibitors in vacuo. Despite neglecting solve nt effects our results correlate reasonably with available experimental dat a and indicate the dominant electrostatic nature of inhibitory effects of P heP derivatives in leucine aminopeptidase and pK(a) shifts resulting from a mino acid substitutions in mutated subtilisins. The range of applicability of the electrostatic approximation has been examined for the chorismate mut ase enzyme.