For this reason, we decided to study the oxidase reaction with QM/MM calculations for an AA10 LPMO containing histidine, glutamine and tyrosine, namely Tf AA10A. We investigate stepwise proton and electron transfers, the possibility of doubly and singly protonated histidine functioning as proton donor, and dissociation of several reaction intermediates from the active-site (see Fig. ). Since large QM regions have recently been shown to be crucial for obtaining accurate results for the mechanism of substrate oxidation we further use considerably larger QM regions in our QM/MM calculations than the previous studies. We compare to these previous studies and highlight some of the differences and similarities in the results section.