The oxyheme complexes of P450cam: A QM/MM study

The substrate bound heme-O2 complexes (ferrous dioxygen, S4 and ferric peroxo, S5) of P450cam (CYP101) have been studied by combined quantum mechanical/molecular mechanical (QM/MM) calculations. The oxyheme (without side chains) is treated with density functional theory and the protein/solvent environment by the CHARMM22 force field. The B3LYP/CHARMM calculations are found to give reasonable descriptions of the oxyheme complexes. An open-shell singlet is predicted to be the ground state for S4 with small energy separations to the excited states. This result is consistent with previous experimental and QM studies. Comparisons with analogous calculations on the isolated QM system in the gas phase show that the protein/solvent environment reduces the open-shell singlet-quintet energy gap which should facilitate the spin inversion upon the binding of the atmospheric oxygen. An intact ferric peroxo complex S5 is found only in the doublet state whereas the quartet and sextet states dissociate upon QM/MM optimization (uncoupling).