Factors That Determine the Variation of Equilibrium and Kinetic Properties of QM/MM Enzyme Simulations: QM Region, Conformation, and Boundary Condition.

ABSTRACT: To analyze the impact of various technical details on the results of quantum mechanical (QM)/molecular mechanical (MM) enzyme simulations, including the QM region size, catechol-O-methyltransferase (COMT) is studied as a model system using an approximate QM/MM method (DFTB3/CHARMM). The results show that key equilibrium and kinetic properties for methyl transfer in COMT exhibit limited variations with respect to the size of the QM region, which ranges from ∼100 to ∼500 atoms in this study. With extensive sampling, local and global structural characteristics of the enzyme are largely conserved across the studied QM regions, while the nature of the transition state (e.g., secondary kinetic isotope effect) and reaction exergonicity are largely maintained. Deviations in the free energy

SUBMITTER: Demapan D 

PROVIDER: S-EPMC9652774 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature