Pharmacophore-directed homology modeling and molecular dynamics simulation of g protein-coupled receptor: Study of possible binding modes of 5-HT2C receptor Agonists
文献类型：期刊论文
| 作者 | Zuo, Zhili; Chen, Gang; Luo, Xiaomin ; Puah, Chummok; Zhu, Weiliang; Chen, Kaixian; Jiang, Hualiang
|
| 刊名 | ACTA BIOCHIMICA ET BIOPHYSICA SINICA
 |
| 出版日期 | 2007-06 |
| 卷号 | 39期号:6页码:413-422 |
| 关键词 | 5-HT2C receptor Flexi-Dock G protein-coupled receptor homology modeling molecular dynamics simulation |
| ISSN号 | 1672-9145 |
| DOI | 10.1111/j.1745-7270.2007.00295.x |
| 文献子类 | Article |
| 英文摘要 | A new pharmacophore-based modeling procedure, including homology modeling, pharmacophore study, flexible molecular docking, and long-time molecular dynamics (MD) simulations, was employed to construct the structure of the human 5-HT2c receptor and determine the characteristics of binding modes of 5-HT2C receptor agonists. An agonist-receptor complex has been constructed based on homology modeling and a pharmacophore hypothesis model based on some high active compounds. Then MD simulations of the ligand-receptor complex in an explicit membrane environment were carried out. The conformation of the 5-HT2C receptor during MD simulation was explored, and the stable binding modes of the studied agonist were determined. Flexible molecular docking of several structurally diverse agonists of the human 5-HT2C receptor was carried out, and the general binding modes of these agonists were investigated. According to the models presented in this work and the results of Flexi-Dock, the involvement of the amino acid residues Asp 134, Ser138, Asn210, Asn331, Tyr358, Ile131, Ser132, Va1135, Thr139, Ile189, Va1202, Va1208, Leu209, Phe214, Va1215, Gly218, Ser219, Phe223, Trp324, Phe327, and Phe328 in agonist recognition was studied. The obtained binding modes of the human 5-HT2C receptor agonists have good agreement with the site-directed mutagenesis data and other studies. |
| WOS关键词 | PARTICLE MESH EWALD ; IDENTIFICATION ; SEROTONIN ; WEIGHT ; 5-HYDROXYTRYPTAMINE(2A) ; ACTIVATION ; KETANSERIN ; RHODOPSIN ; PROGRAM ; BILAYER |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3088077 |
| WOS记录号 | WOS:000247529600004 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273231]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Puah, Chummok |
| 作者单位 | 1.Singapore Polytech, Ctr Biomed & Life Sci, Singapore 13965, Singapore 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Drug Discovery & Design Ct, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zuo, Zhili,Chen, Gang,Luo, Xiaomin,et al. Pharmacophore-directed homology modeling and molecular dynamics simulation of g protein-coupled receptor: Study of possible binding modes of 5-HT2C receptor Agonists[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2007,39(6):413-422. |
| APA | Zuo, Zhili.,Chen, Gang.,Luo, Xiaomin.,Puah, Chummok.,Zhu, Weiliang.,...&Jiang, Hualiang.(2007).Pharmacophore-directed homology modeling and molecular dynamics simulation of g protein-coupled receptor: Study of possible binding modes of 5-HT2C receptor Agonists.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,39(6),413-422. |
| MLA | Zuo, Zhili,et al."Pharmacophore-directed homology modeling and molecular dynamics simulation of g protein-coupled receptor: Study of possible binding modes of 5-HT2C receptor Agonists".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 39.6(2007):413-422. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。