First principles investigation of singly reduced cytochrome P450

1. The application of novel ab initio quantum mechanical methods to the sta tes in the cycle of cytochrome P450 following the first reduction step is d escribed. 2. A good correlation was found between the calculated energy of reduction and the experimentally determined redox potential for a range of substrate- and substrate analogue-bound systems. 3. On reduction of the haem system, the ground state of Fe remains Fe3+. On binding of a CO molecule, Fe adopts a low-spin Fe2+ state, in agreement wi th experiment. However, on binding of an O-2 molecule, calculations indicat e that the system adopts a ferric superoxide ground state, in which the Fe is in a low-spin Fe3+ state.