昆明医科大学学报2026，Vol.47Issue(6)：11-22,12.DOI:10.12259/j.issn.2095-610X.S20260602
基于分子对接筛选肺炎克雷伯菌β-内酰胺金属酶NDM-1抑制剂及活性研究
Molecular Docking-based Screening and Activity Studies of NDM-1 β-Lactamase Inhibitors against Klebsiella Pneumoniae
摘要
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.关键词
计算机辅助筛选/分子对接/分子动力学模拟/NDM-1抑制剂/活性研究Key words
Computer-assisted screening/Molecular docking/NDM-1 inhibitors/Molecular dynamics simulation/Activity study分类
医药卫生引用本文复制引用
杨晓钰,李波,郑瑞,苏敏..基于分子对接筛选肺炎克雷伯菌β-内酰胺金属酶NDM-1抑制剂及活性研究[J].昆明医科大学学报,2026,47(6):11-22,12.基金项目
国家自然科学基金(82460407) （82460407）
云南省第一人民医院新生儿临床重点专科平台开放项目(2024EKKFKT-02) （2024EKKFKT-02）
