Computational study on the selectivity of iron-containing hydroxylase

Here C-H functionalization catalyzed by Iron-containing heme and nonheme were studied, using cytochrome P450 and PtlH as examples. In this work, the C-H activation in the hydroxylation reaction of a model substrate artemisinin catalyzed by three selective P450BM3 variants was studied by combined molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations.

A distinct linear correlation was observed between the barriers of C-H bond activation and the distances between Fe=O oxo and the hydrogen atom to be abstracted. These findings would provide valuable guidance for predicting the reactivity of P450BM3 and other similar reactions where hydrogen abstraction is the rate-limiting step. The second part of the project is the study on non-heme hydroxylase PtlH.