Comparative Molecular Docking Analysis of Carbapenem Antibiotics with Ndm-1 and OXA-23 Β-Lactamases: Insights into Binding Mechanisms

Year 2025, Volume: 15 Issue: 3, 654 - 660, 30.09.2025

Emrah Sarıyer , Gamze Ağırbaş

https://doi.org/10.33808/clinexphealthsci.1675807

Abstract

Objective: This study aimed to investigate the molecular interactions between carbapenem antibiotics (imipenem and meropenem) and two β-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 β-lactamase-mediated antibiotic resistance. The integrated approach validates the utility of computational methods in elucidating molecular interactions and guiding therapeutic strategies.

Keywords

NDM-1 , OXA-23 , imipenem , meropenem , molecular docking

Ethical Statement

This study does not require ethical approval as it involves computational analysis without human or animal subjects.

Supporting Institution

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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