Theoretical Study on Catalytic Reaction of Adenylate Kinase

Abstract

Adenylate kinase is an enzyme which catalyze phosphate transfer amoungst ATP and AMP, and also ADP and ADP. In order to elucidate the nature of the catalytic reaction of adenylate kinase, we carried out theoretical calculations using various level of the theory, Molecular Mechanics, PM3, ab initio, and ONIOM method. With stuructural studies, the reaction is expected to proceed with SN2 like inversion of phosphate group. Two layer ONIOM calculation was performed to acquire structural understanding of phospholylation and reactant, transition state, and product structures were determined with optimization. Our calculation also revealed that the other product which has four terminus ADP oxygen atoms coordinated with Mg2+, was stabler than the product of SN2 like inversion. Also, a few water molecules critical to this reaction is found through molecular dynamics calculation and an explanation for the reaction in which these water molecules participate requires further consideration.