title: Dynamics of an enzymatic substitution reaction in haloalkane dehalogenase.
abstract: Reactive flux molecular dynamics simulations have been carried out using a combined QM/MM potential to study the dynamics of the nucleophilic substitution reaction of dichloroethane by a carboxylate group in haloalkane dehalogenase and in water. We found that protein dynamics accelerates the reaction rate by a factor of 2 over the uncatalyzed reaction. Compared to the thermodynamic effect in barrier reduction, protein dynamic contribution is relatively small. However, analyses of the friction kernel reveal that the origins of the reaction dynamics in water and in the enzyme are different. In aqueous solution, there is significant electrostatic solvation effect, which is reflected by the slow reorganization relaxation of the solvent. On the other hand, there is no strong electrostatic coupling in the enzyme and the major effect on reaction coordinate motion is intramolecular energy relaxation.
authors.affiliation: Department of Chemistry and Supercomputing Institute, Digital Technology Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Kwangho
authors.initials: K
authors.lastname: Nam
authors.forename: Xavier
authors.initials: X
authors.lastname: Prat-Resina
authors.forename: Mireia
authors.initials: M
authors.lastname: Garcia-Viloca
authors.forename: Lakshmi S
authors.initials: LS
authors.lastname: Devi-Kesavan
authors.forename: Jiali
authors.initials: J
authors.lastname: Gao
mesh_terms: D003198:Computer Simulation; D005583:Fourier Analysis; D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D006867:Hydrolases; C046137:haloalkane dehalogenase