Docking-based virtual screening of potential human P2Y12 receptor antagonists
文献类型：期刊论文
| 作者 | Chen, H; Dong, XC; Zhou, MY; Shi, HM; Luo, XP |
| 刊名 | ACTA BIOCHIMICA ET BIOPHYSICA SINICA
 |
| 出版日期 | 2011 |
| 卷号 | 43期号:5页码:400-408 |
| 关键词 | P2Y12 homology modeling virtual screening anti-coagulation |
| 通讯作者 | Luo, XP (reprint author), Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Cardiol, Shanghai 200040, Peoples R China.,luoxp2007@yahoo.com.cn |
| 英文摘要 | Platelet plays essential roles in hemostasis and its dysregulation can lead to arterial thrombosis. P2Y12 is an important platelet membrane adenosine diphosphate receptor, and its antagonists have been widely developed as anticoagulation agents. The current P2Y12 inhibitors available in clinical practice have not fully achieved satisfactory anti-thrombotic effects, leaving room for further improvement. To identify new chemical compounds as potential anticoagulation inhibitors, we constructed a three-dimensional structure model of human P2Y12 by homology modeling based on the recently reported G-protein coupled receptor Meleagris gallopavo beta 1 adrenergic receptor. Virtual screening of the modeled P2Y12 against three subsets of small molecules from the ZINC database, namely lead-like, fragment-like, and drug-like, identified a number of compounds that might have high binding affinity to P2Y12. Detailed analyses of the top three compounds from each subset with the highest scores indicated that all of these compounds beard a hydrophobic bulk supplemented with a few polar atoms which bound at the ligand binding site via largely hydrophobic interactions with the receptor. This study not only provides a structure model of P2Y12 for rational design of anti-platelet inhibitors, but also identifies some potential chemicals for further development. |
| 学科主题 | Biochemistry & Molecular Biology; Biophysics |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biophysics |
| 关键词[WOS] | PROTEIN-COUPLED RECEPTORS ; INDUCED PLATELET ACTIVATION ; DRUG DISCOVERY ; ADP RECEPTORS ; SIGNALING EVENTS ; HOMOLOGY MODELS ; MOLECULAR-BASIS ; AGGREGATION ; BINDING ; TOOL |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000289836200009 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/812]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Chen, H,Dong, XC,Zhou, MY,et al. Docking-based virtual screening of potential human P2Y12 receptor antagonists[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2011,43(5):400-408. |
| APA | Chen, H,Dong, XC,Zhou, MY,Shi, HM,&Luo, XP.(2011).Docking-based virtual screening of potential human P2Y12 receptor antagonists.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,43(5),400-408. |
| MLA | Chen, H,et al."Docking-based virtual screening of potential human P2Y12 receptor antagonists".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 43.5(2011):400-408. |
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