Influence of environment on proton-transfer mechanisms in model triads from theoretical calculations

Abstract

We have carried out theoretical calculations to analyze molecular interactions and proton transfer mechanisms in the formate–imidazole–water system, which may be considered the simplest model of catalytic triads in serine proteases. Computations were carried out at the density functional theory level. The effect of a dielectric environment on energy surfaces is considered using a polarizable continuum model and the self-consistent reaction field approach. The role played by inertial and noninertial polarization of this environment is emphasized. Nonequilibrium solvation effects have been estimated. The results show that there are different reaction mechanisms, concerted or stepwise, that may be competitive, depending on the nature of the molecular environment. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1675–1688, 1998