The cytochromes P450 (P450s) are a superfamily of enzymes which are found in all forms of living organism. They are responsible for the metabolism of many endogenous compounds, participate in the activation/deactivation of many carcinogens and detoxify many xenobiotics. In particular, in humans they metabolise many drugs and hence are of great interest to pharmacologists and toxicologists.
This chapter describes the application of ab initio methods to the study of P450s. There are two principle goals for this investigation. Firstly, ab initio simulations may aid in the understanding of the detailed mechanisms of the interaction of ligand molecules with the active site of an enzyme. The ultimate goal is the development of techniques for the prediction of the outcome of such an interaction. The results presented in this chapter represent the first step along the route to this goal. They demonstrate that the methods applied accurately reproduce experimental observations of the activity of the enzyme and the use of `computational experiments' allows key features of the reaction mechanism to be identified. The cytochrome P450 system offers an ideal first target for ab initio methods as the reaction has a clear signature, described in Section , which may be identified in the results of simulations.
Section gives a brief history of the experimental investigation of the P450 family of enzymes, a summary of the catalytic cycle of P450s as currently understood and some important experimental results and properties of the enzymes. A more complete account of the properties of P450s may be found in the book edited by Omura et al.  or that by Lewis . The approach used for the study of the interactions between ligand molecules and the active site of a P450 is described in Section and the results obtained from the investigation are given in Section . Finally, a summary of this chapter is given in Section .