家蝇钠离子通道的同源模建及分子对接和构效关系  

Homology Modeling of Housefly Voltage-Gated Sodium Ion Channel Receptor and Docking and Three Dimensional Quantitative Structure Activity Relationship

作　　者：颜琦松 舒启超 巨修练[1,2] 

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430074 [2]绿色化工过程教育部重点实验室(武汉工程大学),湖北武汉430074

出　　处：《武汉工程大学学报》2016年第1期10-16,共7页Journal of Wuhan Institute of Technology

摘　　要：利用大鼠脑电压门控钾离子通道DII区的S4-S5片段的结构和古细菌Aeropyrum pernix的钾离子电压门控通道S6区的结构为模板,通过同源模建的方法构建家蝇的钠离子通道受体开启状态的模型,并利用拉氏图和分子动力学分析验证其模型的合理性.将31个拟除虫菊酯类化合物与模建的家蝇钠离子通道受体进行对接研究,并研究其作用机理.结果表明,对接打分与实测活性值相一致,说明了该模型的合理性.通过对接分析和三维定量构效关系实验可以看出,家蝇电压门控钠离子通道上929位苏氨酸与拟除虫菊酯类化合物的羧基形成氢键,且化合物上的氯原子与918位甲硫氨酸具有范德华作用力,同时苯环上增加取代会增加位阻降低化合物活性,邻位和间位取代对化合物活性相对影响较小,而苯环对位取代对活性影响最大,且对位取代基的吸电子能力越强,化合物活性越低.另外,结构与活性关系研究的Co MFA模型与上述对接结果一致.The housefly in an open state sodium channel was homology modeled by using S4-S5 fragment in DIIsection of rat- brain and S6 section of Aeropyrumpernix in voltage- gated potassium channel as structure tem-plates. The model was confirmed by Ramachandran graph and molecular dynamics. Furthermore,two categoriesof 31 pyrethroids were docked with housefly Voltage-gated sodium channel receptor and the docking score fittedwell with the tested activities. The mechanism of insecticide was studied.The results of docking experiment andthe three-dimensional quantitative structure-activity relationship reveal that the 929 Thr of housefly Voltage-gatedsodium channel receptor forms a hydrogen bond with pyrethroid and the chlorine atom on the side chain formsvan der Waals force with Leu925. The effect of substituents on benzene ring may increase the steric hindranceand reduce insecticidal activity. The ortho and meta substitutes of benzene ring have weak effect on activitywhile the para substitute of benzene ring with strong impact on the activity. The COMFA model of the threedimensional quantitative structure activity relationship is in coincidence with docking results.

关 键 词：拟除虫菊酯类化合物 钠离子通道受体 分子对接 3D-QSAR 

分 类 号：R914.2[医药卫生—药物化学]