CDK5与喹啉酮类抑制剂相互作用的分子模拟研究  

Study on Binding of Quinolinone Inhibitors to CDK5 Based on Molecular Dynamics Simulation

作　　者：王伟[1] 曹小宁[1] 顾勇亮[1] 朱小蕾[1] 

机构地区：[1]南京工业大学化学化工学院材料化学工程国家重点实验室,江苏南京210009

出　　处：《南京师大学报（自然科学版）》2013年第2期56-60,共5页Journal of Nanjing Normal University(Natural Science Edition)

基　　金：国家自然科学基金项目(21276122;21136001;20876073)

摘　　要：本文采用分子对接、分子动力学模拟(MD)和结合自由能计算等方法研究了3种喹啉酮类抑制剂与CDK5的相互作用,并且分析和讨论了药物与其周围残基之间的氢键和疏水作用.模拟结果还表明M1和M2与CDK5的结合模式很相似,但残基分解分析表明残基Ile10对于区分M1和M2之间不同的生物活性起到关键的作用.然而,M3的结合模式与M1或M2相比却有一些不同,其中它与残基Asn144之间的静电作用在结合过程中起到了关键的作用.本文的工作对于以后设计新型的有较高选择性的CDK5抑制剂具有一定的指导意义.Molecular docking, molecular dynamics （MD） simulations, and binding free energy analysis are performed to investigate the interactions between three quinolinone inhibitors and CDK5. The hydrogen bonding and hydrophobic interactions between inhibitors and adjacent residues are analyzed and discussed. The results illustrate that the binding modes of M1 and M2 with CDK5 are quite similar. And the energy decomposition analysis reveals that the residue I10 is one key residue for the different bioaetivity between M1 and M2. I-Iowever,M3 in M3/CDK5 exhibits a different binding mode compared to M1 or M2 ,the electrostatic energy between M3 and residue Asn144 plays a key role in the binding. The results of our work may be helpful for the design of novel and selective CDK5 inhibitors.

关 键 词：喹啉酮类抑制剂 细胞色素依赖蛋白激酶-5 分子动力学模拟 结合自由能 

分 类 号：O643.1[理学—物理化学]