Large-scale QM/MM free energy simulations of enzyme catalysis reveal the influence of charge transfer.

ABSTRACT: Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations provide key insights into enzyme structure-function relationships. Numerous studies have demonstrated that large QM regions are needed to systematically converge ground state, zero temperature properties with electrostatic embedding QM/MM. However, it is not well known if ab initio QM/MM free energy simulations have this same dependence, in part due to the hundreds of thousands of energy evaluations required for free energy estimations that in turn limit QM region size. Here, we leverage recent advances in electronic structure efficiency and accuracy to carry out range-separated hybrid density functional theory free energy simulations in a representative methyltransferase. By studying 200 ps of ab initio QM/MM dynamics for

SUBMITTER: Kulik HJ 

PROVIDER: S-EPMC6085747 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature