Two Sides of Quantum-Based Modeling of Enzyme-Catalyzed Reactions: Mechanistic and Electronic Structure Aspects of the Hydrolysis by Glutamate Carboxypeptidase.

ABSTRACT: We report the results of a computational study of the hydrolysis reaction mechanism of N-acetyl-l-aspartyl-l-glutamate (NAAG) catalyzed by glutamate carboxypeptidase II. Analysis of both mechanistic and electronic structure aspects of this multistep reaction is in the focus of this work. In these simulations, model systems are constructed using the relevant crystal structure of the mutated inactive enzyme. After selection of reaction coordinates, the Gibbs energy profiles of elementary steps of the reaction are computed using molecular dynamics simulations with ab initio type QM/MM potentials (QM/MM MD). Energies and forces in the large QM subsystem are estimated in the DFT(PBE0-D3/6-31G**) approximation. The established mechanism includes four elementary steps with the activation energy b

SUBMITTER: Krivitskaya AV 

PROVIDER: S-EPMC8538779 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature