To validate this mechanism, we started our QM/MM calculations by optimizing a representative MD snapshot from the simulation of variant 2. The snapshot was chosen based on the closest distance between the benzylic pro-R(H) of substrate and N1 of nitrenoid. An energy scanning was carried out for abstracting the pro-R(H) and leading to the formation of a highly reactive intermediate complex as well as a radical substrate. Subsequent energy scanning resulted in product formation via rebound mechanism as found in native P450 enzymes. The energy profile diagram and the key geometries are organized in Figure .