The cytochromes P450 (CYPs) are an important family of enzymes involved in the metabolism of drugs. The prediction of the selectivity of CYP-mediated metabolism will assist in the avoidance of adverse drug reactions. A detailed understanding of the factors that govern the s selectivity is of fundamental importance to the development of predictive models. Selectivity of CYP enzymes is p partially attributed to the relative reactivity of different functional groups of a substrate with respect to the active oxidizing species, compound I. A combined quantum mechanical/molecular mechanical (QM/MM) approach has been employed to model the chemoselectivity of alkene oxidation in P450cam. Two model compounds were used, yielding relative energy barriers that are consistent with experiment.