The largest increase in energetics between the two hydration states is calculated for orientation III, where the barriers increase by 9.6 and 5.6 kcal/mol for imipenem and meropenem, respectively, when the hydration state is changed. For the lower barriers, OQ1 and O Q2 form on average 2.0 (± 0.1) and 1.4 (± 0.1) hydrogen bonds, respectively, for the imipenem and meropenem complexes, while for the higher barriers the equivalent numbers are 2.8 (± 0.1) and 2.1 (± 0.2, data not shown).