Additionally, orientation II might hinder the positioning of the DW in the active site in proximity to the electrophilic acyl carbon. For 93% and 87%, respectively, of the simulation times for the imipenem and meropenem acylenzymes in orientation II, the distance between the AC electrophilic carbon and the closest water molecule falls beyond 4 Å (an arbitrary threshold distance for a feasible nucleophilic attack; Figure ). This is likely due to the 6α-hydroxyethyl methyl group partly occupying the space in the binding pocket for the deacylating water molecule, and thereby forcing this water further away from the AC. This is reflected in deposited crystal structures, as a DW candidate that is suitably positioned for nucleophilic attack is not observed in any OXA-48/carbapenem complex. In a previous study (mainly based on molecular dynamics), orientation II was observed to obstruct the positioning of the DW in the active site. Docquier et al. concluded that only a slight repositioning of the methyl group of the 6α-hydroxyethyl sidechain is needed to better accommodate a water molecule at a suitable distance for nucleophilic attack.