title: Direct dynamics calculations of reaction rate and kinetic isotope effects in enzyme catalysed reactions.
abstract: Direct dynamics calculations employing hybrid quantum mechanical and molecular mehanical (QM/MM) potentials and molecular dynamics simulation methods have been used to explore the important dynamic role that enzyme structure has on proton transfer in the C-H bond breakage of a methylamine substrate by methylamine dehydrogenase (MADH). Canonical variational transition state theory with optimised multidimensional tunnelling corrections has been used to predict deuterium kinetic isotope effects corresponding to a range of enzyme conformations and to show the importance of donor acceptor separation, and transition state and product stabilisation within the active site. Large kinetic isotope effects can be predicted for proton transfer with both semi-empirical and ab initio electronic structure methods.
authors.affiliation: Department of Chemistry, University of Manchester, UK M13 9PL.
authors.forename: Gary
authors.initials: G
authors.lastname: Tresadern
authors.forename: Sara
authors.initials: S
authors.lastname: Nunez
authors.forename: Paul F
authors.initials: PF
authors.lastname: Faulder
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Ian H
authors.initials: IH
authors.lastname: Hillier
authors.forename: Neil A
authors.initials: NA
authors.lastname: Burton
mesh_terms: D004798:Enzymes / Q000737:chemistry / Q000378:metabolism; D007554:Isotopes; D007700:Kinetics; D008744:Methylamines / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009038:Motion; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004798:Enzymes; D007554:Isotopes; D008744:Methylamines; C021567:methylamine dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors