Molecular Docking-Based Screening and Activity Studies of NDM-1 β-Lactamase Inhibitors against Klebsiella pneumoniae

Xiaoyu YANG; Bo LI; Rui ZHENG; Min SU

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Xiaoyu YANG, Bo LI, Rui ZHENG, Min SU. Molecular Docking-Based Screening and Activity Studies of NDM-1 β-Lactamase Inhibitors against Klebsiella pneumoniae[J]. Journal of Kunming Medical University.

Citation:

Xiaoyu YANG, Bo LI, Rui ZHENG, Min SU. Molecular Docking-Based Screening and Activity Studies of NDM-1 β-Lactamase Inhibitors against Klebsiella pneumoniae[J]. Journal of Kunming Medical University.

Xiaoyu YANG, Bo LI, Rui ZHENG, Min SU. Molecular Docking-Based Screening and Activity Studies of NDM-1 β-Lactamase Inhibitors against Klebsiella pneumoniae[J]. Journal of Kunming Medical University.

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Molecular Docking-Based Screening and Activity Studies of NDM-1 β-Lactamase Inhibitors against Klebsiella pneumoniae

Xiaoyu YANG^{1, 2},
Bo LI¹,
Rui ZHENG¹,
Min SU^{1
,
,}

1.
Department of Clinical Laboratory
2.
Regenerative Medicine Research Center，The First People’s Hospital of Yunnan Province，Kunming Yunnan 650032，China

Received Date: 2025-11-10
Available Online: 2026-01-20

Abstract

Abstract

Objective To screen potential inhibitors based on the three-dimensional structure of NDM-1 enzyme and evaluate their pharmacological activity. Methods Computer-aided drug design methods were employed to screen the top 5 candidate compounds with the highest molecular docking scores from the 50K Diversity Library. The minimum inhibitory concentration （MIC） was further determined in combination with meropenem, imipenem, and ceftazidime to assess their inhibitory activity against NDM-1. The stability of the candidate compounds binding to NDM-1 was analyzed through molecular dynamics simulation. Results When the top 5 compounds with the highest molecular docking scores were combined with three β-lactam antibiotics, the MIC values showed no significant reduction, suggesting limited inhibitory effects on NDM-1. Molecular dynamics simulation revealed that compounds 1, 3, 4, and 5 exhibited large root-mean-square deviation （RMSD） and free energy fluctuations in the reaction system, indicating unstable conformations; although compound 2 showed no significant RMSD fluctuation, its binding free energy value was relatively low, potentially resulting in insufficient binding affinity. Conclusion Differences in binding stability between the five candidate compounds and NDM-1 protein led to their overall limited inhibitory activity.
- Computer-assisted screening,
- Molecular docking,
- NDM-1 inhibitors,
- Molecular dynamics simulation,
- Activity study

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References(21)

References

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