How Large Should the QM Region Be in QM/MM Calculations? The Case of Catechol O-Methyltransferase.

ABSTRACT: Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations are widely used in studies of enzymatic catalysis. Until recently, it has been cost prohibitive to determine the asymptotic limit of key energetic and structural properties with respect to increasingly large QM regions. Leveraging recent advances in electronic structure efficiency and accuracy, we investigate catalytic properties in catechol O-methyltransferase, a prototypical methyltransferase critical to human health. Using QM regions ranging in size from reactants-only (64 atoms) to nearly one-third of the entire protein (940 atoms), we show that properties such as the activation energy approach within chemical accuracy of the large-QM asymptotic limits rather slowly, requiring approximately 500-600 atoms if the QM resid

SUBMITTER: Kulik HJ 

PROVIDER: S-EPMC5108028 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature