A Scaffold-Independent Subcellular Event-Based Analysis: Characterization of Significant Structural Modifications

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• 作者：Ying-Ting Lin ; Guan-Yu Chen
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2012
• 出版时间：February 27, 2012
• 年：2012
• 卷：52
• 期：2
• 页码：506-514
• 全文大小：372K
• 年卷期：v.52,no.2(February 27, 2012)
• ISSN：1549-960X

文摘

General and singular subcellular events within the ligand-dependent receptor-mediated cellular response were separated by using the Jurs and the electrotopological state (ES) descriptors, allowing characterization of the significant structural modifications in a given set of collected peroxisome proliferator-activated receptor 纬 (PPAR纬) agonists. The identified Jurs descriptor is the integrated function of all the general events but is scaffold-dependent. The top captured ES descriptors stand for significant structural modifications, i.e., singular events. To further elucidate the descriptor-event relationship, three biological data sets show that the Jurs descriptor can be further divided into three important descriptors, the log D, polar surface area, and shape-like descriptor. The identification of the essential descriptors for general events is the first regression, and the prioritization of all the possible structural modifications of the 46 collected thiazolidinedione PPAR纬 agonists is the second regression. As results, the top captured ES symbols can correspond to the singular ligand鈥搑eceptor interactions as highlighted in the X-ray crystallographic image of rosiglitazone鈥揚PAR纬 complex.