For LPMOs in general (and particularly for LsAA9A), H2O2 has shown to be the (only) co-substrate. Therefore, we start by discussing substrate-free and substrate-bound structures with H2O2 replacing the equatorial water or chloride in Cu(I) and Cu(I)-Cell-Cl -, respectively (note that neither the water nor the chloride are coordinated in these structures). We aim to obtain the same pre-bound state as Lim et al. (indicated as Cu(I)…H2O2 in Figure ), but in one case additionally include a substrate (Cu(I)-Cell…H2O2 in Figure ). In the pre-bound state, H2O2 is not coordinated to Cu(I), but instead located in the pocket between the substrate and active site, where it is stabilized by interactions with a second-sphere histidine and glutamine (see His147 and Gln162 in Figure ). We observe that substrate binding brings H2O2 closer to copper (Cu-O distance of 2.54 Å and 2.39 Å in Cu(I)…H2O2 and Cu(I)-Cell…H2O2, respectively) and increases the O-O bond in ), which is consistent with the difference of 1.1-1.4 eV reported by Lim et al. We also find that the dx2-y2-orbital (see Figure ) is the HOMO in Cu(I)…H2O2.