中文摘要：

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.

英文摘要：

Acinetobacter baumannii is one of the most common pathogenic bacteria in hospital with severe antibiotics resistance. LpxC has been extensively studied as a new antibacterial drug target. However, structure based on drug design was not possible due to the lack of crystallographic data of Acinetobacter baumanniiLpxC protein. In the current study, we established the 3D structure of Acinetobacter baumannii LpxC based on the crystal structure of Pseudomonas aeruginosa LpxC. The accuracy of the homology modeling was supported by ramachandran plot distribution and Profile-3D analyses. The model was further optimized by molecular dynamics simulation to improve some unreasonable conformations. Molecular docking results showed that the S configuration of the benzyloxyacetohydroxamic acids inhibitors can bind to the shallow pocket involving residues F191, H237 and K238, which might be the key factor to determine their inhibitory effect.