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

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• 作者：Nan Zheng ; Jiagao Cheng ; Wei Zhang ; Weihua Li ; Xusheng Shao ; Zhiping Xu ; Xiaoyong Xu ; Zhong Li
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2014
• 出版时间：November 5, 2014
• 年：2014
• 卷：62
• 期：44
• 页码：10646-10653
• 全文大小：509K
• ISSN：1520-5118

文摘

Fipronil, which targets GABA_A receptors (GABA_ARs), 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 GABA_ARs from fruitfly and zebrafish systems. It was found that, in the zebrafish system, the H-bond between 6鈥睺hr 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鈥睞la 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_ARs, which might be helpful in designing selective insecticides against pests instead of fishes.

Keywords:

fipronil; GABA_A receptors; homology modeling; docking; molecular dynamics simulation