Dynamics of an Enzymatic Substitution Reaction in Haloalkane Dehalogenase

Department of Chemistry and Supercomputing Institute, Digital Technology Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 03/2004; 126(5):1369-76. DOI: 10.1021/ja039093l
Source: PubMed


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.

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Available from: Mireia Garcia-Viloca, May 08, 2015
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    • "We have not considered time-scales for the H and other motions. An example of a use of classical dynamics in the TS region is seen in Nam et al. (2004). In virtue of a Discussion in this symposium, it is useful to recall the basic assumptions of classical mechanical TST. "
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