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论文类型：期刊论文

发表时间：2011-08-01

发表刊物：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录刊物：Scopus、SCIE、PubMed

卷号：12

期号：8

页面范围：5011-5030

ISSN号：1422-0067

关键字：5-HT6; 3D-QSAR; CoMFA; CoMSIA; molecular dynamics

摘要：5-HT6 receptor has been implicated in a series of diseases including anxiety, depression, schizophrenia and cognitive dysfunctions. 5-HT6 ligands have been reported to play a significant role in the treatment for central nervous system (CNS) diseases. Presently, a large series of 223 5-HT6 ligands were studied using a combinational method by 3D-QSAR, molecular docking and molecular dynamics calculations for further improvement of potency. The optimal 3D models exhibit satisfying statistical results with r(ncv)(2), q(2) values of 0.85 and 0.50 for CoMFA, 0.81 and 0.53 for CoMSIA, respectively. Their predictive powers were validated by external test set, showing r(pred)(2) of 0.71 and 0.76. The contour maps also provide a visual representation of contributions of steric, electrostatic, hydrophobic and hydrogen bond fields as well as the prospective binding models. In addition, the agreement between 3D-QSAR, molecular docking and molecular dynamics simulation proves the rationality of the developed models. These results, we hope, may be helpful in designing novel and potential 5-HT6 ligands.