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鲍曼不动杆菌已成为最普遍的医院致病菌,且耐药情况严峻.LpxC作为新抗菌药物靶点被大量研究,但鲍曼不动杆菌LpxC晶体尚未解析得到,基于其结构的药物设计等工作无法开展.以铜绿假单胞菌LpxC晶体结构为模板,通过同源模建方法获得鲍曼不动杆菌LpxC结构模型.较好的Ramachandran plot分布和Profile-3D结果验证了模型的合理性.用分子动力学模拟优化鲍曼不动杆菌LpxC模型,修补部分不合理构象.后续分子对接结果显示S构型的苄氧乙酰基羟肟酸类抑制剂比R构型分子能更有效地结合在F191,H237和K238组成的较浅口袋中,这可能是S构型抑制剂活性更高的主要因素,模拟结果与实验数据吻合较好.
Acinetobacter baumannii has become the most common hospital pathogenic bacteria, and the drug resistance is severe.LpxC as a new antimicrobial drug targets have been extensively studied, but Acinetobacter baumannii LpxC crystal has not been resolved, based on the structure of the drug design Etc. The LpxC structure model of Acinetobacter baumannii was obtained by using the LpxC crystal structure of Pseudomonas aeruginosa as a template and the homology modeling method was used.A good Ramachandran plot distribution and Profile-3D results verify the rationality of the model .Molecular dynamics simulation was used to optimize the LpxC model of Acinetobacter baumannii to repair part of the unreasonable conformation.The subsequent docking results showed that the benzyloxyacetyl hydroxamic acid inhibitors of S configuration could bind more effectively than those of R configuration In the shallow pocket consisting of F191, H237 and K238, this may be the main reason for the higher activity of S-configuration inhibitor. The simulation results are in good agreement with the experimental data.