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论文类型：期刊论文

发表时间：2012-04-01

发表刊物：JOURNAL OF MOLECULAR GRAPHICS & MODELLING

收录刊物：PubMed、SCIE、EI

卷号：34

期号：34

页面范围：76-88

ISSN号：1093-3263

关键字：Protein kinase C theta; CoMFA; CoMSIA; 3D-QSAR; Molecular docking; Molecular dynamics

摘要：Presently, an in silico modeling was carried out on a large series of 263 PKCO inhibitors using 3D-QSAR, molecular docking and molecular dynamics (MD) simulations for the first time. Based on different alignment rules, several computational models were established with their statistical results compared. The resultant models derived from the database alignment exhibit satisfying internal and external predictive capabilities with q(2) of 0.503, 0.616 and r(pred)(2) of 0.568, 0.602 for CoMFA and CoMSIA, respectively. The consistency of conclusion among 3D contour maps of CoMFA and CoMSIA, molecular docking and molecular dynamics proves the reliability of the developed models. The analysis of the 3D contour plots permits interesting conclusions about the effects of different substituent groups at different positions of the common scaffold. In addition, Leu461 and Asn509 have been identified as the key amino acid residues to form H-bond interaction with the ligand compound. The developed models will provide a clue to the design of novel PKC theta inhibitors. (C) 2012 Elsevier Inc. All rights reserved.