The highest point on the PES was subjected to full transition state (TS) optimization using the dimer method implemented in the dl-find module of Chemshell3.7. TS structures were validated by frequency calculations. Only one unique imaginary frequency was present, with the normal mode of the imaginary frequency corresponding to the transition of the hydrogen atom from the C-H bond of the O-Me to be demethylated to the oxygen atom of the Fe(IV)=O of the Cpd I. All the QMMM calculations of the WT-CYP450GcoA and its variants calculations started from the Cpd I , the main oxidant in P450 mediated reactions. The hydrogen atom abstraction and the rebound step were studied for all the variants at S=1/2.