Previously, our QM/MM simulations indicated that Leu158 may play an important role in modulating active site hydration in the deacylation of ceftazidime by OXA-48-like enzymes. The orientation of Leu158 also differed initially between the two OXA-48/carbapenem systems, as the Cβ -Cγ bond has rotated by 180° in the meropenem structure. To study if Leu158 has a similar effect on carbapenem hydrolysis as observed for ceftazidime, its rotamers were first investigated by measuring the χ1 dihedral (N-Cα-Cβ-Cγ) in MM MD simulations. The distribution of sampled rotamers is presented in Figure . After the heating phase, Leu158 essentially always rotates away from the crystallographic g-orientation (χ1 ≈ 290°) to the t orientation (χ1 ≈ 180°) to allow space for the 6α-hydroxyethyl moiety, which in turn also permits for two water molecules to form hydrogen bonds with Lys73:OQ1. As the cephalosporin scaffold lacks a functional group similar to the 6αhydroxyethyl group of carbapenems, typically bearing larger substituents in the β orientation at the equivalent 7-position, it is likely that Leu158 does not possess a similar role in carbapenem hydrolysis to that suggested for cephalosporins.