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[1]颜琦松,舒启超,巨修练*.家蝇钠离子通道的同源模建及分子对接和构效关系[J].武汉工程大学学报,2016,38(1):10-16.[doi:10. 3969/j. issn. 1674-2869. 2016. 01. 002]
　YAN Qisong,SHU Qichao,JU Xiulian.Homology Modeling of Housefly Voltage?Gated Sodium Ion Channel Receptor and Docking and Three Dimensional Quantitative Structure Activity Relationship[J].Journal of Wuhan Institute of Technology,2016,38(1):10-16.[doi:10. 3969/j. issn. 1674-2869. 2016. 01. 002]
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家蝇钠离子通道的同源模建及分子对接和构效关系(/HTML)
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
38
期数:
2016年1期
页码:
10-16
栏目:
化学与化学工程
出版日期:
2016-03-07

文章信息/Info

Title:
Homology Modeling of Housefly Voltage?Gated Sodium Ion Channel Receptor and Docking and Three Dimensional Quantitative Structure Activity Relationship
文章编号:
1674-2869(2016)01-0010-07
作者:
颜琦松1; 2; 舒启超1; 2; 巨修练1; 2*
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
Author(s):
YAN Qisong1; 2 ;  SHU Qichao1; 2;  JU Xiulian1; 2
1.School of Chemical Engineering &Pharmacy， Wuhan Institute of Technology， Wuhan 430074，China； 2.Key Laboratory for Green Chemical Process（Wuhan Institute of Technology），Ministry of Education， Wuhan 430074，China
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
Keywords:
pyrethroid;  voltage-gated sodium channel receptor;  molecular docking;  3D-QSAR
分类号:
R914.2
DOI:
10. 3969/j. issn. 1674-2869. 2016. 01. 002
文献标志码:
A
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CoMFA模型与上述对接结果一致.
Abstract:
The housefly in an open state sodium channel was homology modeled by using S4?S5 fragment in DII section of rat?brain and S6 section of Aeropyrumpernix in voltage?gated potassium channel as structure templates. The model was confirmed by Ramachandran graph and molecular dynamics. Furthermore， two categories of 31 pyrethroids were docked with housefly Voltage?gated sodium channel receptor and the docking score fitted well with the tested activities. The mechanism of insecticide was studied.The results of docking experiment and the three?dimensional quantitative structure?activity relationship reveal that the 929Thr of housefly Voltage?gated sodium channel receptor forms a hydrogen bond with pyrethroid and the chlorine atom on the side chain forms van der Waals force with Leu925. The effect of substituents on benzene ring may increase the steric hindrance and reduce insecticidal activity. The ortho and meta substitutes of benzene ring have weak effect on activity while the para substitute of benzene ring with strong impact on the activity. The COMFA model of the three dimensional quantitative structure activity relationship is in coincidence with docking results.

参考文献/References:

［1］　SALGADO V L，NARAHASHI T. Immobilization of sodium?channel gating charge in crayfish giant?axons by the insecticides fenvalerate［J］. Molecular pharmacology， 1993， 43（4）：626-634. ［2］　VIJVERBERG H P，VAN DEN BERCKEN. Neurotoxicological effects and the mode of action of pyrethroid insecticides［J］. Critical reviews in toxicology， 1990， 21（2）：105-126. ［3］　BIOOMQUIST J R. Ion channels as target for insecticide［J］. Annu review entomology， 1996， 41（1）：163-190. ［4］　WILLIAMSON M S， MARTINEZ-TORRES， DHICK C A， et al. Identification of mutations in the housefly para-type sodium channel gene associated with knockdown resistance （kdr） to pyrethroid insecticides［J］. Molecular and gennel genetics， 1996， 252（1）：51-60. ［5］　LEE S H， SODERLUND D M. The V410M mutation associated with pyrethroid resistance in Heliothis virescens reduces the pyrethroid sensitivity of housefly sodium channels expressed in Xenopusoocytes［J］. Insect biochemistry& molecular biology， 2001，31（1）：19-29. ［6］　TAN J G， LIU Z Q， WANG R W， et al. Identification of amino acid residues in the insect sodium channel critical for pyrethroid binding［J］. Molecular pharmacology， 2005， 67（2）：513-522. ［7］　DING S H ， INGLEBY L， AHERN C A， et al. Investigating the putative glycine hinge in Shaker potassium channel［J］. Journal of general physiology， 2005， 126（3）：213-226. ［8］　 NEEDLEMAN S B，WUNSCH C D. Ageneral method applicable to the search for similarities in the amino acid sequence of two proteins［J］. Journal of molecular biology， 1970， 48（3）：443-453. ［9］　 WANG J M，WOLF R M，CALDWELL J W，et al. Development and testing of ageneral amber forcefield［J］. Journal of computational chemistry， 2004， 25（9）：1157- 1174. ［10］　CORRINGERPJ，BAADENM，BOCQUETN，et al. Atomic structure and dynamics of pentameric ligand?gated ion channels： new insight from bacterial homologues［J］. The journal of physiology， 2001， 588（4）：565-572. ［11］　CHENLG，DURKINKA，CASIDAJ E. Structure model for γ-aminobutyric acid receptor noncompetitive antagonist binding： widely diverse structure fit the same site［J］. Proceedings of the national academy of science of the united stated of america， 2006， 103（13）：5185- 5190. ［12］　CRAMER R D，PATTERSON D E，BUNCE J D.Comparative molecular field analysis （COMFA）. Effect of shape on binding of steroids to carrier proteins［J］. Journal of the american chemical society， 1988， 110（18）：5959-5967. ［13］　HOU T J ，XU X J. Progress on CoMFA research ［J］. Progress in chemistry， 2001， 13（6）：436-440. ［14］　MITEVA M，LEE W H，MONTES M，et al. Fast structure-based virtual ligand screening combining FRED，DOCK， and Surflex［J］. Journal of medicinal chemistry， 2005， 48 （19）：6012-6022. ［15］　CHENG J，JU X L，CHEN X Y，et al. Homology modeling of human 1，2 and house fly 3 GABA receptor channels and Surflex-docking of fipronil［J］. Journal of molecular modeling， 2009， 15（9）：1145-1153.

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备注/Memo

备注/Memo:
收稿日期：2015-11-13作者简介：颜琦松，硕士研究生. E-mail：[email protected] *通讯作者：巨修练，博士，教授. E-mail： [email protected]
更新日期/Last Update: 2016-02-27