For the case of Meropenem, it can interact with almost the same residues as Imipenem. As can be seen from Fig. 3C , the binding pocket for Meropenem involves six residues, of which Glu88 and Thr126 form three hydrogen bonds with the antibiotic drug. Since there is one more five-member ring in Meropenem (Fig. 3C) , some additional hydrogen bonds are needed to stabilize the ligand during the process of cleaving its amide bond and inactivate the antibiotic drug. Based on these structural findings and previous theoretical studies [56, 57, 58] , we proposed a catalytic mechanism for NDM-1, as illustrated in Fig. 4 . In our model, the metalbinding Asp60 acts as the general base that activates the water nucleophile, while the protonation of Asp60 results in the cleavage of its bond to the metal ion. Figure S4 The QMEAN score components calculated based on the Z-score of each component in comparison with the average xray structures.