Investigation of the Structure Requirement for 5-HT6 Binding Affinity of Arylsulfonyl Derivatives: A Computational Study

International Journal of Molecular Sciences

Ming Hao²  Yan Li¹  Hanqing Li² 

[1] Department of Materials Science and Chemical Engineering, Dalian University of Technology, Dalian 116023, Liaoning, China;

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

DOI  :  10.3390/ijms12085011

来源: mdpi

【 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 r²_ncv, q² 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 r²_pred 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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.