Toward understanding the molecular basis for chemical allosteric modulator design
文献类型：期刊论文
| 作者 | Wang, Qi1,2; Zheng, Mingyue3 ; Huang, Zhimin2; Liu, Xinyi2; Zhou, Huchen1; Chen, Yingyi2; Shi, Ting2; Zhang, Jian2
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| 刊名 | JOURNAL OF MOLECULAR GRAPHICS & MODELLING
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| 出版日期 | 2012-09 |
| 卷号 | 38页码:324-333 |
| 关键词 | Allosteric regulation Allosteric modulators Structural rigidity "Allosteric-like" rule |
| ISSN号 | 1093-3263 |
| DOI | 10.1016/j.jmgm.2012.07.006 |
| 文献子类 | Article |
| 英文摘要 | Among the regulation mechanisms of cellular function, allosteric regulation is the most direct, rapid and efficient. Due to the wider receptor selectivity and lower target-based toxicity, compared with orthosteric ligands, allosteric modulators are expected to play a larger role in pharmaceutical research and development. However, current difficulties, such as a low affinity and unknown structural features of potential allosteric small-molecules, usually obstruct the discovery of allosteric modulators. In this study, we compared known allosteric modulators with various compounds from different databases to unveil the structural and qualitative characteristics of allosteric modulators. The results show that allosteric modulators generally contain more hydrophobic scaffolds and have a higher structural rigidity, i.e., less rotatable bonds and more rings. Based on this analysis, an empirical rule was defined to determine the structural requirements for an allosteric modulator. It was found that a large proportion of allosteric modulators (80%) can be successfully retrieved by this "allosteric-like" filter, which shows good discriminatory power in identifying allosteric modulators. Therefore, the study provides deeper insight into the chemical properties of allosteric modulators and has a good potential for the design or optimization of allosteric compounds. (C) 2012 Elsevier Inc. All rights reserved. |
| WOS关键词 | ION-CHANNEL ACTIVITY ; PROTEIN ; PHOSPHORYLATION ; BINDING |
| 资助项目 | Foundation for the Author of National Excellent Doctoral Dissertation of PR China[201083] ; National Natural Science Foundation of China[21002062] ; National Natural Science Foundation of China[81001399] ; Innovative Research Team of Shanghai Municipal Education Commission[00000000] ; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning[00000000] ; Shanghai PuJiang Program[10PJ406800] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Computer Science ; Crystallography ; Mathematical & Computational Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000313392800033 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277947]  |
| 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 | Zhang, Jian |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China; 2.Shanghai Jiao Tong Univ, Dept Pathophysiol, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ,Sch Med, Shanghai 200025, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Qi,Zheng, Mingyue,Huang, Zhimin,et al. Toward understanding the molecular basis for chemical allosteric modulator design[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2012,38:324-333. |
| APA | Wang, Qi.,Zheng, Mingyue.,Huang, Zhimin.,Liu, Xinyi.,Zhou, Huchen.,...&Zhang, Jian.(2012).Toward understanding the molecular basis for chemical allosteric modulator design.JOURNAL OF MOLECULAR GRAPHICS & MODELLING,38,324-333. |
| MLA | Wang, Qi,et al."Toward understanding the molecular basis for chemical allosteric modulator design".JOURNAL OF MOLECULAR GRAPHICS & MODELLING 38(2012):324-333. |
入库方式： OAI收割
来源：上海药物研究所
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