- ASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks. [PMID: 26365237]
Qiancheng Shen, Guanqiao Wang, Shuai Li, Xinyi Liu, Shaoyong Lu, Zhongjie Chen, Kun Song, Junhao Yan, Lv Geng, Zhimin Huang, Wenkang Huang, Guoqiang Chen, Jian Zhang
Nucleic acids research 2016:44(D1)
3 Citations (Google Scholar as of 2016-02-02)
Abstract: Allosteric regulation, the most direct and efficient way of regulating protein function, is induced by the binding of a ligand at one site that is topographically distinct from an orthosteric site. Allosteric Database (ASD, available online at http://mdl.shsmu.edu.cn/ASD) has been developed to provide comprehensive information featuring allosteric regulation. With increasing data, fundamental questions pertaining to allostery are currently receiving more attention from the mechanism of allosteric changes in an individual protein to the entire effect of the changes in the interconnected network in the cell. Thus, the following novel features were added to this updated version: (i) structural mechanisms of more than 1600 allosteric actions were elucidated by a comparison of site structures before and after the binding of an modulator; (ii) 261 allosteric networks were identified to unveil how the allosteric action in a single protein would propagate to affect downstream proteins; (iii) two of the largest human allosteromes, protein kinases and GPCRs, were thoroughly constructed; and (iv) web interface and data organization were completely redesigned for efficient access. In addition, allosteric data have largely expanded in this update. These updates are useful for facilitating the investigation of allosteric mechanisms, dynamic networks and drug discoveries. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
- ASD v2.0: updated content and novel features focusing on allosteric regulation. [PMID: 24293647]
Zhimin Huang, Linkai Mou, Qiancheng Shen, Shaoyong Lu, Chuangang Li, Xinyi Liu, Guanqiao Wang, Shuai Li, Lv Geng, Yaqin Liu, Jiawei Wu, Guoqiang Chen, Jian Zhang
Nucleic acids research 2014:42(Database issue)
29 Citations (Google Scholar as of 2016-01-26)
Abstract: Allostery is the most direct and efficient way for regulation of biological macromolecule function and is induced by the binding of a ligand at an allosteric site topographically distinct from the orthosteric site. AlloSteric Database (ASD, http://mdl.shsmu.edu.cn/ASD) has been developed to provide comprehensive information on allostery. Owing to the inherent high receptor selectivity and lower target-based toxicity, allosteric regulation is expected to assume a more prominent role in drug discovery and bioengineering, leading to the rapid growth of allosteric findings. In this updated version, ASD v2.0 has expanded to 1286 allosteric proteins, 565 allosteric diseases and 22 008 allosteric modulators. A total of 907 allosteric site-modulator structural complexes and >200 structural pairs of orthosteric/allosteric sites in the allosteric proteins were constructed for researchers to develop allosteric site and pathway tools in response to community demands. Up-to-date allosteric pathways were manually curated in the updated version. In addition, both the front-end and the back-end of ASD have been redesigned and enhanced to allow more efficient access. Taken together, these updates are useful for facilitating the investigation of allosteric mechanisms, allosteric target identification and allosteric drug discovery.
- ASD: a comprehensive database of allosteric proteins and modulators. [PMID: 21051350]
Zhimin Huang, Liang Zhu, Yan Cao, Geng Wu, Xinyi Liu, Yingyi Chen, Qi Wang, Ting Shi, Yaxue Zhao, Yuefei Wang, Weihua Li, Yixue Li, Haifeng Chen, Guoqiang Chen, Jian Zhang
Nucleic acids research 2011:39(Database issue)
62 Citations (Google Scholar as of 2016-01-26)
Abstract: Allostery is the most direct, rapid and efficient way of regulating protein function, ranging from the control of metabolic mechanisms to signal-transduction pathways. However, an enormous amount of unsystematic allostery information has deterred scientists who could benefit from this field. Here, we present the AlloSteric Database (ASD), the first online database that provides a central resource for the display, search and analysis of structure, function and related annotation for allosteric molecules. Currently, ASD contains 336 allosteric proteins from 101 species and 8095 modulators in three categories (activators, inhibitors and regulators). Proteins are annotated with a detailed description of allostery, biological process and related diseases, and modulators with binding affinity, physicochemical properties and therapeutic area. Integrating the information of allosteric proteins in ASD should allow for the identification of specific allosteric sites of a given subtype among proteins of the same family that can potentially serve as ideal targets for experimental validation. In addition, modulators curated in ASD can be used to investigate potent allosteric targets for the query compound, and also help chemists to implement structure modifications for novel allosteric drug design. Therefore, ASD could be a platform and a starting point for biologists and medicinal chemists for furthering allosteric research. ASD is freely available at http://mdl.shsmu.edu.cn/ASD/.