Pharmacophore and Docking-based 3D-QSAR Studies on HIV-1 Integrase Inhibitors

doi:10.1007/s40242-014-3395-5

高等学校化学研究 ›› 2014, Vol. 30 ›› Issue (2): 297-305.doi: 10.1007/s40242-014-3395-5

Pharmacophore and Docking-based 3D-QSAR Studies on HIV-1 Integrase Inhibitors

ZHANG Xiaoyi¹, DENG Dongjie¹, TAN Jianjun¹, HE Yu², LI Chunhua¹, WANG Cunxin¹

1. College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, P. R. China;
2. College of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, P. R. China

收稿日期:2013-09-17 修回日期:2013-12-02 出版日期:2014-04-01 发布日期:2014-01-23
通讯作者: LI Chunhua, WANG Cunxin E-mail:cxwang@bjut.edu.cn;chunhuali@bjut.edu.cn
基金资助:
Supported by the National Natural Science Foundation of China(Nos.31100523, 31171267, 21173014) and the Beijing Outstanding Personnel Training Foundation, China(No.2012D005015000006).

Pharmacophore and Docking-based 3D-QSAR Studies on HIV-1 Integrase Inhibitors

ZHANG Xiaoyi¹, DENG Dongjie¹, TAN Jianjun¹, HE Yu², LI Chunhua¹, WANG Cunxin¹

1. College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, P. R. China;
2. College of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, P. R. China

Received:2013-09-17 Revised:2013-12-02 Online:2014-04-01 Published:2014-01-23
Contact: LI Chunhua, WANG Cunxin E-mail:cxwang@bjut.edu.cn;chunhuali@bjut.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(Nos.31100523, 31171267, 21173014) and the Beijing Outstanding Personnel Training Foundation, China(No.2012D005015000006).

摘要/Abstract

摘要：

Integrase(IN) plays an essential role in the process of HIV-1 replication. IN inhibitors of diketo acid derivatives(DKAs) were analysed by the Comparative Molecular Field Analysis(CoMFA) and Comparative Molecular Similarity Induces Analysis(CoMSIA) methods. A set of 42 compounds were randomly selected as the training set(35) and test set(7). Firstly, a good pharmacophore(goodness of hit=0.787) was obtained and used to align ligands. Then, predictive models were constructed with the CoMFA and CoMSIA methods based on the pharmacophore alignment. As a result, the CoMSIA method yielded the best model with an r² of 0.955 and a q² of 0.665, which can predict the activities of the tested DKAs very well(r²=0.559). Finally, DKAs were docked into IN, and the predicit modes were superimposed on the contour maps obtained from the best CoMSIA model. The superimposed maps gave a visualized and meaningful insight into the inhibitory behaviors, providing significantly useful information for the rational drug design of anti-IN agents.

关键词: HIV-1 integrase, Diketo acid, Quantitative structure-activity relationship, Pharmacophore, Molecular docking

Abstract:

Key words: HIV-1 integrase, Diketo acid, Quantitative structure-activity relationship, Pharmacophore, Molecular docking

ZHANG Xiaoyi, DENG Dongjie, TAN Jianjun, HE Yu, LI Chunhua, WANG Cunxin. Pharmacophore and Docking-based 3D-QSAR Studies on HIV-1 Integrase Inhibitors[J]. 高等学校化学研究, 2014, 30(2): 297-305.

ZHANG Xiaoyi, DENG Dongjie, TAN Jianjun, HE Yu, LI Chunhua, WANG Cunxin. Pharmacophore and Docking-based 3D-QSAR Studies on HIV-1 Integrase Inhibitors[J]. Chemical Research in Chinese Universities, 2014, 30(2): 297-305.

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Pharmacophore and Docking-based 3D-QSAR Studies on HIV-1 Integrase Inhibitors

Pharmacophore and Docking-based 3D-QSAR Studies on HIV-1 Integrase Inhibitors

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