Pharmacophore-directed Homology Modeling and Molecular Dynamics Simulation of G Protein-coupled Receptor: Study of Possible Binding Modes of 5-HT_(2C) Receptor Agonists
文献类型：期刊论文
| 作者 | Zhili ZUO1; Gang CHEN1; Xiaomin LUO2; Chummok PUAH1; Weiliang ZHU1 ; Kaixian CHEN1; Hualiang JIANG1
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| 刊名 | Acta Biochimica et Biophysica Sinica
 |
| 出版日期 | 2007 |
| 卷号 | 39期号:6页码:413 |
| 关键词 | PARTICLE MESH EWALD IDENTIFICATION SEROTONIN WEIGHT 5-HYDROXYTRYPTAMINE(2A) ACTIVATION KETANSERIN RHODOPSIN PROGRAM BILAYER 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 |
| 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. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/286036]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院上海药物研究所 2.新加坡理工学院 |
| 推荐引用方式 GB/T 7714 | Zhili ZUO,Gang CHEN,Xiaomin LUO,et al. Pharmacophore-directed Homology Modeling and Molecular Dynamics Simulation of G Protein-coupled Receptor: Study of Possible Binding Modes of 5-HT_(2C) Receptor Agonists[J]. Acta Biochimica et Biophysica Sinica,2007,39(6):413. |
| APA | Zhili ZUO.,Gang CHEN.,Xiaomin LUO.,Chummok PUAH.,Weiliang ZHU.,...&Hualiang JIANG.(2007).Pharmacophore-directed Homology Modeling and Molecular Dynamics Simulation of G Protein-coupled Receptor: Study of Possible Binding Modes of 5-HT_(2C) Receptor Agonists.Acta Biochimica et Biophysica Sinica,39(6),413. |
| MLA | Zhili ZUO,et al."Pharmacophore-directed Homology Modeling and Molecular Dynamics Simulation of G Protein-coupled Receptor: Study of Possible Binding Modes of 5-HT_(2C) Receptor Agonists".Acta Biochimica et Biophysica Sinica 39.6(2007):413. |
入库方式： OAI收割
来源：上海药物研究所
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