show that these water molecules are involved in strong hydrogen bonds to hydrogens protonating axial O4. In 5-O, H10 is strongly hydrogen bonded to His404 (i.e., ρ(H10-N26)= 0.03733) and H6 is hydrogen bonded to a water molecule with ρ=0.06714 electrons/bohr 3 . In comparing kcal/mol although O2 is unprotonated and O1 is diprotonated. In the case of 18-O, there are also steric clashes between H8 and H23 and a hydrogen bond forms between H8 and N40 (ρ(H8-N40)=0.03398) of Arg490. This steric clash becomes evident with space filling models (Figure ). With any model, one can notice how H23 has been pushed out of the guanidine plane (Figure ).