文献类型：期刊文献

英文题名：Binding Difference of Fipronil with GABAARs in Fruitfly and Zebrafish: Insights from Homology Modeling, Docking, and Molecular Dynamics Simulation Studies

作者：Zheng, Nan[1];Cheng, Jiagao[1,2];Zhang, Wei[1];Li, Weihua[2];Shao, Xusheng[1];Xu, Zhiping[1];Xu, Xiaoyong[1];Li, Zhong[1,3]

机构：[1]E China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Sch Pharm, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[3]Shanghai Collaborat Innovat Ctr Biomfg, Shanghai 200237, Peoples R China

年份：2014

卷号：62

期号：44

起止页码：10646

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20144600180922);WOS:【SCI-EXPANDED(收录号:WOS:000344516700004)】；

基金：This work was financially supported by the National Key Technology R&D Program of China (2011BAE06B05), the National Natural Science Foundation of China (21172070), the National High Technology Research Development Program of China (2011AA10A207), and the Fundamental Research Funds for the Central Universities (222201314006)

语种：英文

外文关键词：fipronil; GABA(A) receptors; homology modeling; docking; molecular dynamics simulation

摘要：Fipronil, which targets GABAA receptors (GABAARs), is the first phenylpyrazole insecticide widely used in crop protection and public hygiene. However, its high toxicity on fishes greatly limited its applications. In the present study, a series of computational methods including homology modeling, docking, and molecular dynamics simulation studies were integrated to explore the binding difference of fipronil with GABAARs from fruitfly and zebrafish systems. It was found that, in the zebrafish system, the H-bond between 6'Thr and fipronil exerted key effects on the recognition of fipronil, which was absent in the fruitfly system. On the other hand, in the fruitfly system, strong electrostatic interaction between 2'Ala and fipronil was favorable to the binding of fipronil but detrimental to the binding in the zebrafish system. These findings marked the binding difference of fipronil with different GABA(A)Rs, which might be helpful in designing selective insecticides against pests instead of fishes.