Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists
Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists
复制标题
氮杂环类 CCR5 拮抗剂的 3D-QSAR 建模与分子对接联合研究
DOI：
10.1016/j.molstruc.2013.03.062
复制
发表时间：
2013-08-06
影响因子：
3.8
通讯作者：
Lin, Zhihua
中科院分区：
文献类型：
--
作者：
Ji, Yongjun;Shu, Mao;Lin, Zhihua
The beta chemokine receptor 5 (CCR5) is an attractive target for pharmaceutical industry in the HIV-1, inflammation and cancer therapeutic areas. In this study, we have developed quantitative structure activity relationship (QSAR) models for a series of 41 azacycles CCR5 antagonists using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and Topomer CoMFA methods. The cross-validated coefficient q(2) values of 3D-QASR (CoMFA, CoMSIA, and Topomer CoMFA) methods were 0.630, 0.758, and 0.852, respectively, the non-cross-validated R-2 values were 0.979, 0.978, and 0.990, respectively. Docking studies were also employed to determine the most probable binding mode. 3D contour maps and docking results suggested that bulky groups and electron-withdrawing groups on the core part would decrease antiviral activity. Furthermore, docking results indicated that H-bonds and pi bonds were favorable for antiviral activities. Finally, a set of novel derivatives with predicted activities were designed. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.
