Quantum mechanical/molecular mechanical analysis of mechanisms of enzyme action. Human acetylcholinesterase

The influence of the system separation into the QM and MM parts on the result of quantum mechanical/molecular mechanical (QM/MM) modeling of acetylcholine hydrolysis in the acetylcholinesterase active site was considered. The minimum acceptable quantum subsystem that provides an adequate description of the enzymatic reaction energy profile was identified. The computed energy profiles were analyzed and possible inaccuracies in QM/MM calculations were estimated. The fairly high tetrahedral intermediate stability was demonstrated, which is in a good agreement with the newest experimental observations.