Emrah Sarıyer, Gamze Ağırbaş
Clinical and Experimental Health Sciences - 2025;15(3):654-660
Objective: This study aimed to investigate the molecular interactions between carbapenem antibiotics (imipenem and meropenem) and two beta-lactamase enzymes, NDM-1 (class B) and OXA-23 (class D), to understand the structural basis of carbapenem resistance. Methods: The study employed molecular docking methods using the crystal structures and homology models of the NDM-1 and OXA-23 enzymes to analyze binding affinities and interaction patterns. Results: The results revealed distinct binding characteristics for each enzyme. NDM-1 exhibited a polar, hydrophobic active site, with imipenem forming hydrogen bonds with ASP124, ASN220, and LYS211, while meropenem relied on weaker interactions like Van der Waals forces. In contrast, OXA-23 featured a hydrophobic cavity with charged residues, where imipenem bonded with ARG259 and meropenem interacted with SER79, TRP219, and ARG259. A key finding was the significantly lower binding energy for the OXA-23-imipenem complex in the crystal structure (-8.06 kcal/mol) compared to its homology model (-5.34 kcal/mol), highlighting the importance of accurate structural representation. The study demonstrated strong agreement between the computational and experimental data. Conclusion: These findings provide critical insights into the structural basis of carbapenem resistance, offering potential avenues for designing inhibitors to combat beta-lactamase-mediated antibiotic resistance. The integrated approach validates the utility of computational methods in elucidating molecular interactions and guiding therapeutic strategies.
