The use of ab initio quantum mechanical calculations will allow the mechanism of interaction of P450 with its substrate to be modelled. This in turn will allow theories regarding unknown features of human P450 to be tested and predictions to be made of the result of an interaction of a substrate with a given P450.
The combination of the techniques outlined in Section 2 with the use of massively parallel supercomputers has made ab initio calculations on this scale feasible for the first time.
Cytochrome P450 is an ideal target for these calculations. The gross reaction mechanism, summarised in Section 5.2, is thought to be well understood, however there is currently no reliable method for the prediction of the outcome of the interaction of a given substrate with a P450 enzyme. The ability to make such predictions would be of enormous benefit to pharmacologists as P450 plays a vital rôle in the metabolism of drugs. The possibility of `designer' P450s will also be opened. These could be created to recognise and oxidise specific compounds, for example toxic organic pollutants allowing bacterial hosts to be used to clean up environmental pollution.
This chapter has outlined a challenging investigative program designed to work towards these goals. It is anticipated that this will form the core research that will be submitted as a PhD thesis.