中文关键词:INSTIs三维定量构效关系分子对接分子动力学模拟 英文关键词:INSTIsthree-dimensional quantitative structure-activity relationshipsmolecular dockingmolecular dynamics simulation 基金项目:

作者	单位	E-mail
刘冬琳	广州中医药大学中药学院 广州	2531046039@qq.com
刘鹰翔	广州中医药大学中药学院 广州	liuyingxiang@gzucm.edu.cn
李耿	广州中医药大学中药学院 广州
马玉卓	广东药科大学药学院 广州
曾巧玲	广州中医药大学中药学院 广州

摘要点击次数:1256 全文下载次数:0 中文摘要: 为了获得高活性、结构新颖的INST抑制剂，本文采用CoMFA和CoMSIA两种方法对32个萘啶类INST抑制剂进行了三维定量构效关系的研究，并建立了相关模型，其交叉验证系数分别为q2=0.809和q2=0.816，拟合验证系数分别为r2=0.998和r2=0.981，表明所建立的模型是可靠的且具有一定的预测能力。利用分子对接探讨小分子化合物与INST蛋白的相互作用模式，结合模式表明，萘啶类化合物主要通过疏水作用和氢键作用与INSTIs蛋白结合。最后通过分子动力学模拟进一步验证对接结果，发现对接的结合模式与分子动力学模拟得到的结果是一致的。本研究获得的综合模型和推论可以为开发有效的HIV整合酶链转移抑制剂提供重要的理论基础。 英文摘要: In order to obtain highly active, novel INST inhibitors. In this paper, three-dimensional quantitative structure-activity relationship of 32 naphthyridine INST inhibitors were studied using CoMFA and CoMSIA leading to reliable models. The cross-validation coefficients were q2=0.809 and q2=0.816, the Fitting verification coefficients were r2=0.998 and r2=0.981, indicating the predictive ability of the established models. Molecular docking was also performed to investigate the binding mode of small molecule compounds to INSTIs. The binding mode indicates that naphthyridines bind to INSTIs mainly via hydrophobic interactions and hydrogen bonding. Finally, the docking results were further verified by molecular dynamics simulation, and it was found that the binding mode of the docking was consistent with the results obtained by molecular dynamics simulation. The comprehensive models and inferences obtained in this study can provide an important theoretical basis for the development of new and effective HIV integrase chain transfer inhibitors. 查看全文查看/发表评论下载PDF阅读器 相关附件：版权转让声明书 -->