For the H 2 O 2 -driven pathway, we found that this pathway is feasible, in agreement with previous investigations. 36,37 A suitable QM region is also important for this pathway and we find slightly higher barriers than several previous investigations. Thus, the HAA from Throughout the reaction, His147 and Gln162 form important hydrogen bonds to the oxygen species bound to Cu, and these two residues thus appear crucial in stabilizing transition states and intermediates important to the mechanism.