中文摘要：

肺炎克雷伯碳青霉烯酶能水解临床治疗多药耐药菌感染的碳青霉烯类抗生素，严重削弱革兰氏阴性菌感染的治疗效果．开发新型有效专一的肺炎克雷伯碳青霉烯酶抑制剂有助于提高此类抗生素的治疗有效率．β-内酰胺酶抑制蛋白能竞争性抑制肺炎克雷伯碳青霉烯酶的活性．通过粗粒化模型分析肺炎克雷伯碳青霉烯酶β-内酰胺酶抑制蛋白复合物的运动模式．结果表明，结合β-内酰胺酶抑制蛋白后，肺炎克雷伯碳青霉烯酶的运动模式发生较大变化．使用分子对接和分子动力学模拟方法得到一系列环硼酸类β-内酰胺酶抑制剂与肺炎克雷伯碳青霉烯酶的结合模式，并从氢键和能量的角度解释该类抑制剂的识别机制与构象-抑制活性间的关系．本研究为后续基于肺炎克雷伯碳青霉烯酶结构的抑制剂设计提供了一定的理论依据．

英文摘要：

Carbapenems, used in clinical treatment of multi-drug resistance bacterial infection, can be hydrolyzed by Klebsiella pneurnoniae carbapenemases, which weaken the treatment effect of gram negative bacterial infection. It＇s an important means to develop novel, potent and specific Klebsiella pneumoniae carbapenemase inhibitors for improving the efficiency of these antibiotics in clinical treatment. And β- lactamase inhibitor protein can competitively inhibits the activity of Klebsiella pneumoniae carbapenema- ses. The movement patterns of complex involved in KZebsiella pneumoniae carbapenemase and β-lactamase inhibitor protein are analyzed by coarse-grained models. The results indicate the movement pat- terns of Klebsiella pneumoniae carbapenemase change obviously after inhibited by β-lactamase inhibitor protein. Then, the binding modes between the series of cyclic boronic acid β-lactamase inhibitors andKlebsiella pneurnoniae carbapenemase are released through the ways of molecular docking and molecular dynamics simulation, and the relationship between the recognition mechanism and conformation-inhibition activity of these inhibitors are explained from the angle of hydrogen bonds and energy. This research provides a theoretical basis of the subsequent design of the inhibitor based on the Klebsiella pneumoniae earbapenemase structure.