|本期目录/Table of Contents|

[1]巨修练,钱程.γ-氨基丁酸受体同源模建及与黄酮类化合物的分子对接[J].武汉工程大学学报,2014,(08):10-15.[doi:103969/jissn16742869201408002]
　JU Xiu lian,Qian Cheng.Homology modeling and docking with flavonoids of human γaminobutyric acid receptor[J].Journal of Wuhan Institute of Technology,2014,(08):10-15.[doi:103969/jissn16742869201408002]
点击复制

γ-氨基丁酸受体同源模建及与黄酮类化合物的分子对接(/HTML)
分享到：

《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
期数:
2014年08期
页码:
10-15
栏目:
化学与化学工程
出版日期:
2014-08-31

文章信息/Info

Title:
Homology modeling and docking with flavonoids of human γaminobutyric acid receptor
文章编号:
16742869(2014)08001006
作者:
巨修练; 钱程
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):
JU Xiulian1; 2;  Qian Cheng1; 2
1．School of Chemical Engineering and 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:
黄酮类化合物; γ氨基丁酸受体; 分子对接
Keywords:
flavonoid ;  γaminobutyric acid receptor ;  docking
分类号:
R914.2
DOI:
103969/jissn16742869201408002
文献标志码:
A
摘要:
为研究更有效的γ氨基丁酸受体激动剂，以海兔烟碱乙酰胆碱结合蛋白（PDB登记号2XYS，0.194 nm）作为模板，运用同源模建的方法构建人γ氨基丁酸A型受体模型，并利用拉氏图和分子动力学分析验证其模型的合理性.将41个黄酮类化合物与模建的人γ氨基丁酸A型受体进行对接研究，对接打分与实测活性值相吻合.黄酮类化合物与人γ氨基丁酸A型受体对接结果显示，黄酮类化合物的母环分别与190位酪氨酸和140位酪氨酸形成共轭，降低体系能量并使体系稳定，验证了模型的合理性.此外，3’位对黄酮类化合物活性的影响至关重要，尤其引入硝基时活性明显提高.38号化合物的对接打分最高，也说明相应的增加取代基个数有利于提高该类化合物活性.
Abstract:
To develop more effective γAminobutyric acid receptor agonist, type A human γAminobutyric acid receptor was built by the homology modeling using the cryoelectron microscopy of the acetylcholine binding protein of Aplysia californica as a template. The rationality of the models was confirmed by Ramachandran graph and molecular dynamics. Furthermore, 41 flavonoids were docked into type A human γAminobutyric acid receptor and the docking score fitted with the testing activity. The results of the docking experiment reveal that Tyr140 and Tyr190 conjugated with flavonoids reduce the energy of the system，which demonstrates the rationality of the homology mode. Moreover, position 3’ has an important influence on the activity of flavonoids, especially as nitro added. The docking score of number 38 compound is highest, which demonstrates that the increase of substituent brings higher activity of the compounds.

参考文献/References:

［1］ARGYROPOULOS S V, NUTT D. The use of benzodiazepines in,anxiety and other disorders ［J］. The journal of the European College of Neuropsychopharmacology, 1999, 9 (6): 407412.［2］VIOLA H, MARDER M, WOLFMAN C, et al. 6Bromo3’nitroflavone, a new high affinity benzodiazepine receptor agonist recognizes two populations ofcentral cortical binding sites ［J］. Bioorganic and Medicinal Chemistry Letters, 1997, 7 (3): 373378.［3］CRISTINA W, MARIEL M. Flavonoids as GABAA receptor ligands:the whole story［J］. Journal of Experimental Pharmacology, 2012, 4: 924.［4］MARSHALL G R, MAYER D, NAYLOR C B, et al. Mechanismbased analysis of enzyme inhibitors of amide bond hydrolysis ［J］. Progress in Clinical and biological research, 1989, 291: 287295.［5］ZHU Z Y, SALI A, BLUNDELL T L. A variable gap penalty function and feature weights for protein 3D structure comparisons ［J］. Protein Engineering, 1992, 5 (1): 4351.［6］BRAMS M, PANDYA A, KUZMIN D, et al. A structural and mutagenic blueprint for molecular recognition of strychnine and dtubocurarine by different cysloop receptors ［J］. PloS Biology, 2011, 9 (3): 11001034.［7］NEEDLEMAN S B，WUNSCH C D. A general 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.［8］WANG J M, WOLF R M, CALDWELL J W, et al. Development and testing of a general amber force field ［J］. Journal of Computational Chemistry, 2004, 25 (9): 11571174.［9］RUPPERT J, WELCH W, JAIN AN. Automatic identification and representation of protein binding sites for molecular docking ［J］. Protein Science, 1997, 6 (3): 524533.［10］巨修练，王黎丽，李科.斑马鱼A型γ氨基丁酸受体同源模建及分子对接［J］.武汉工程大学学报，2013（6）：2029.JU Xiulian, WANG Lili, LI Ke. Homology modeling and docking of zebrafish γaminobutyric acid receptor ［J］. Journal of Wuhan Institute of Technology, 2013 (6):2029.(in Chinese)［11］CRAMER R D, PATTERSON D E, BUNCE J D. Recent advances in comparative molecular field analysis (CoMFA) ［J］. Progress in Clinical and Biological, 1989, 291: 161165.［12］CORRINGER P J, BAADEN M, BOCQUET N, 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［13］CHEN L G, DURKIN K A, CASIDA J E. Structure model for gamma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.［14］MITEVA M A, LEE W H, MONTES M O, 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 Jin, JU Xiulian, CHEN Xiangyang, et al. Homology modeling of human α1β2γ2 and house fly β3 GABA receptor channels and Surflexdocking of fipronil ［J］. Journal of Molecular Modeling, 2009, 15: 11451153.

相似文献/References:

[1]吴聪华,程华,李琳玲,等.药用植物黄酮类化合物的提取方法[J].武汉工程大学学报,2011,(09):34.
　WU Conghua,CHENG Hua,et al. Extracting techniques and analysis methods forflavonoids in medicinal plants[J].Journal of Wuhan Institute of Technology,2011,(08):34.

备注/Memo

备注/Memo:
收稿日期：20140630作者简介：巨修练（1959），男，陕西乾县人，教授，博士，博士研究生导师. 研究方向：药物构效关系.
更新日期/Last Update: 2014-09-16