Computational approaches to cytochrome P450 function

The action of cytochrome P450 (P450) enzymes has been for years a very active arena of research that led to important insights, and generated lively debates over the nature of the various species and their reactivity patterns¹. The active species of the enzyme is based on an iron ligated to a protoporphyrin IX macrocycle and two additional axial ligands (Figure 2.1): one, called proximal, is a thiolate from a cysteinate side chain of the protein and the other, called distal, is a variable ligand that changes during the cycle. When the distal ligand becomes an oxo group, the species is called Compound I (Cpd I), which is the reactive species of the enzyme and one of the most potent oxidants known in nature.