Abstract
We review density functional theory studies of various types of reactions performed by the cytochrome P450 family of enzymes. We describe the various reactions on equal footing with an emphasis on models to predict sites of metabolism for an arbitrary molecule. The activation barriers range between 0 and 109 kJ/mol, depending more on the atoms surrounding the reactive site than on the type of reaction. Therefore, the intrinsic reactivity can rather well be predicted by simple chemical rules. However, for a full predictive model, the steric effects of the enzyme surrounding the heme group also need to be modeled, which is often harder.
Keywords: Cytochromes P450, heme, density functional theory, QM/MM.
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