With the triprotonated and quadprotonated input structures, one of these hydrogens transfers to His404 (N26) in many cases. The key difference between QM Region I and II is that QM Region II has an additional crystallographic water molecule "above" vanadate. Thus, above the vanadate there is a row of three water molecules which form a series of hydrogen bonds between Asp292 and vanadate. Although this row is also formed with only two water molecules in the case of QM Region I, the distances from O4 to O15 and O16 are increased in the case of QM Region II because of this row of water molecules; hence H6 or H7 becomes hydrogen bonded to N26 of His404 (with an average ρ=0.046). In some cases, such as 15-O (Figure ) or 16-O (Figures 6),