Ab initio hybrid quantum mechanical/molecular mechanical studies of the mechanisms of the enzymes protein kinase and thymidine phosphorylase

Hybrid quantum mechanical/molecular mechanical (QM/MM) models have been used to explore the mechanisms of enzyme catalysis. We discuss the role of the conserved aspartate in a protein kinase and of Lys-190 in the catalytic activity of the E. coli form of thymidine phosphorylase. We have used both ab initio Hartree-Fock and density functional based methods and note the inadequacy of schemes based on semi-empirical QM methods to properly describe the active site of these systems. (C) 2000 Elsevier Science B.V. All rights reserved.