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Hydrogen Abstraction of Camphor Catalyzed by Cytochrome P450cam: A QM/MM Study
1Department of Chemistry and Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln , Lincoln, Nebraska 68588-0304, United States.
Abstract:
A combined quantum mechanics and molecular mechanics (QM/MM, QM = UB3LYP-D3, MM = AMBER) method is used to study the hydrogen abstraction reaction in P450cam catalyzed hydroxylation of camphor in the quartet state. Compared to QM/MM calculations in the literature, this study uses larger basis sets for the most important atoms at the active site and QM/MM Hessian harmonic frequency calculations to determine the standard Gibbs free energy of activation and kinetic isotope effect. The QM/MM covalent boundary is treated with a capping hydrogen atom method, which is simple and robust. An energy barrier of 21.3 kcal/mol and a standard free energy of activation of 16.8 kcal/mol are obtained for this hydrogen abstraction reaction. These values are similar to those reported in the literature, suggesting that when a general protocol is followed, QM/MM results are reproducible. It is found that using a sufficiently large basis set is important to minimize basis set errors.
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