Reaction pathway and free-energy barrier for reactivation of dimethylphosphoryl-inhibited human acetylcholinesterase.

ABSTRACT: The dephosphorylation/reactivation mechanism and the corresponding free-energy profile of the dimethylphosphoryl-inhibited conjugate of human acetylcholinesterase (AChE) has been studied by performing first-principles quantum mechanical/molecular mechanical free-energy (QM/MM-FE) calculations. On the basis of the QM/MM-FE results, for the favorable reaction pathway, the entire dephosphorylation/reactivation process consists of three reaction steps, including the nucleophilic water attack on the P atom, the spatial reorganization of the dimethylphosphoryl group, and the dissociation between the dimethylphosphoryl group and Ser203 of AChE. The overall free-energy barrier for the entire dephosphorylation/reactivation reaction is found to be the free-energy change from the initial reactant to

SUBMITTER: Liu J 

PROVIDER: S-EPMC2795121 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature