The main stabilizing interactions between the inhibitor and the protein include hydrogen bonds of the phosphonate group with Arg120 and Asn210, and stacking with the aromatic Phe62 and Tyr67 residues. The bromine substitution in the R 3 position remained in close proximity to the His240 indicating a stabilizing interaction between the σ-hole of the halogen and the electron-rich π-cloud of the histidine. These findings are also in line with Pemberton et al. As a result a bridging water molecule and not hydroxide ion will be used in all subsequent MM calculations.