title: Atomistic insight into the origin of the temperature-dependence of kinetic isotope effects and H-tunnelling in enzyme systems is revealed through combined experimental studies and biomolecular simulation.
abstract: The physical basis of the catalytic power of enzymes remains contentious despite sustained and intensive research efforts. Knowledge of enzyme catalysis is predominantly descriptive, gained from traditional protein crystallography and solution studies. Our goal is to understand catalysis by developing a complete and quantitative picture of catalytic processes, incorporating dynamic aspects and the role of quantum tunnelling. Embracing ideas that we have spearheaded from our work on quantum mechanical tunnelling effects linked to protein dynamics for H-transfer reactions, we review our recent progress in mapping macroscopic kinetic descriptors to an atomistic understanding of dynamics linked to biological H-tunnelling reactions.
authors.affiliation: Manchester Interdisciplinary Biocentre and Faculty of Life Science, University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.
authors.forename: Sam
authors.initials: S
authors.lastname: Hay
authors.forename: Christopher
authors.initials: C
authors.lastname: Pudney
authors.forename: Parvinder
authors.initials: P
authors.lastname: Hothi
authors.forename: Linus O
authors.initials: LO
authors.lastname: Johannissen
authors.forename: Laura
authors.initials: L
authors.lastname: Masgrau
authors.forename: Jiayun
authors.initials: J
authors.lastname: Pang
authors.forename: David
authors.initials: D
authors.lastname: Leys
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sutcliffe
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Scrutton
mesh_terms: D003198:Computer Simulation; D004798:Enzymes / Q000737:chemistry*; D007554:Isotopes; D007700:Kinetics; D008958:Models, Molecular; D013696:Temperature
chemical_list: D004798:Enzymes; D007554:Isotopes