The lower barrier (in colour) corresponds to a state with only one water molecule hydrogen bonded to Lys73:OQ2, and one or two waters hydrogen bonded to Lys73:OQ1 while the higher barrier corresponds to a state with two water molecules hydrogen bonded to both carboxylate oxygens (Figure , carboxylate oxygens labelled in Scheme 1). For all hydration states, the calculated barriers follow the same trend of I < II < III, i.e. the lowest barriers are calculated for orientation I.