摘要：氟虫腈作为一种苯基吡唑类农药，它杀虫谱广，药效高。它作用于害虫的GABA-A受体，影响氯离子通道。近年来有大量报道显示该杀虫剂不仅对农业害虫有杀灭作用，还会对如蜜蜂、水生生物等会产生毒性。本实验通过分子进化、同源建模和分子对接方法，阐明氟虫腈对害虫、蜜蜂、水生生物有毒杀作用，而对人畜低毒的机理。该结果为开发环境友好杀虫剂提供了一条思路。我们主要的研究内容如下：
（1）从数据库中搜集不同生物的GABA-A受体蛋白质序列，选取氟虫腈防治对象之一的二化螟的序列与其他生物的序列逐一进行全序列对比。研究发现序列相似度与毒性呈现正相关。
（2）建立分子进化树，发现害虫、蜜蜂和水生生物的GABA-A受体的亲缘性关系近，而人等哺乳动物与害虫的亲缘关系远。结果表明亲缘性近的毒性高，远的毒性低。
（3）寻找到氟虫腈与GABA-A受体结合的核心序列片段并进行比对，结果发现与二化螟核心序列相似度高的物种，氟虫腈对其毒性高。
（4）利用同源建模构建二化螟、蜜蜂和人的GABA-A受体三文结构，运用分子对接手段研究氟虫腈与上述三个受体的结合方式。结果表明氟虫腈与二化螟和蜜蜂的结合方式一致，而与人的完全不同。这一对接结果可以解释氟虫腈对害虫和蜜蜂有毒性，而对人低毒。20590
毕业论文关键词：氟虫腈；GABA受体；分子进化；同源建模；分子对接
The relationship between GABA receptor molecular evolution and the toxicity of Fipronil
Abstract:As a Phenylpyrazole pesticides , fipronil has broad spectrum insecticide , it may affect agricultural pest GABA-A receptor normal activities of the chloride channel effect . In recently years, a large number of reports indicate that the drug not only kill agricultural pests , but also on such as bees , aquatic organisms, In this study, we use molecular evolution, homology modeling and molecular docking method to clarify fipronil on insects, bees, aquatic organisms have toxic effects, and low toxicity to humans and other animals. The result is the development of environmentally friendly insecticides provides a way. Our main contents are as follows :
(1) Collect different organisms GABA-A receptor protein sequences from the database. Select one of fipronil main control object Chilo suppressalis sequence to one by one compare to other creature sequence to find the sequence identity positively correlated with toxicity.
(2) Establish molecular evolution tree to find the GABA-A receptor affinity relationships between pest bee and aquatic organism, to human, the kinship is far away from pest, The results showed that high affinity have toxicity but low are not.
(3) To find the fipronil binding on Chilo suppressalis core sequence fragments and comparing to other species. We can conclude that which species have high identity with core sequence, That species will more affected by fipronil.
(4) Use homology modeling to build Chilo suppressalis, Apis mellifera, Homo sapiens GABA-A receptor 3D structure, and by molecular docking to observe the mode of drug bind with the receptor. The result shows that fipronil dock to the Chilo suppressalis is the same as Apis mellifera, and it is different from Homo sapiens, it can explain the drug effect the pest and bee but not effect the human.
Key word: Fipronil; GABA receptor; Molecular evolution; Homology modeling; Molecular docking
目录
引言 1
1 文献综述 2
1.1 氟虫腈 2
1.1.1 氟虫腈的简介 2
1.1.2 氟虫腈的应用 2
1.1.3 氟虫腈的健康毒性 2 GABA受体分子进化规律与氟虫腈毒性关系研究:http://www.youerw.com/yixue/lunwen_12428.html