Combined quantum mechanical–molecular mechanical study of catalysis by the enzyme phospholipase A2: an investigation of the potential energy surface for amide hydrolysis

Abstract

A combined ab initio molecular orbital–molecular mechanical computational model has been applied to the investigation of the potential energy surface of catalysis by the enzyme phosphoiipase A₂. By the integration of molecular mechanical and quantum mechanical gradients, the model allows the geometry optimisation of a substrate within the environment of the active site. The method has been applied to a comparison of the mechanisms of ester and amide hydrolysis by phospholipase A₂. An estimation of the transition state for amide hydrolysis is described.