Int. J. Mol. Sci. 2011, 12(8), 5011-5030; doi:10.3390/ijms12085011
Article

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

Ming Haoemail, Yan Li* email, Hanqing Liemail and Shuwei Zhangemail
Department of Materials Science and Chemical Engineering, Dalian University of Technology, Dalian 116023, Liaoning, China
* Author to whom correspondence should be addressed.
Received: 8 July 2011; in revised form: 19 July 2011 / Accepted: 29 July 2011 / Published: 8 August 2011
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Abstract: 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 r2ncv, 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 r2pred 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.
Keywords: 5-HT6; 3D-QSAR; CoMFA; CoMSIA; molecular dynamics

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MDPI and ACS Style

Hao, M.; Li, Y.; Li, H.; Zhang, S. Investigation of the Structure Requirement for 5-HT6 Binding Affinity of Arylsulfonyl Derivatives: A Computational Study. Int. J. Mol. Sci. 2011, 12, 5011-5030.

AMA Style

Hao M, Li Y, Li H, Zhang S. Investigation of the Structure Requirement for 5-HT6 Binding Affinity of Arylsulfonyl Derivatives: A Computational Study. International Journal of Molecular Sciences. 2011; 12(8):5011-5030.

Chicago/Turabian Style

Hao, Ming; Li, Yan; Li, Hanqing; Zhang, Shuwei. 2011. "Investigation of the Structure Requirement for 5-HT6 Binding Affinity of Arylsulfonyl Derivatives: A Computational Study." Int. J. Mol. Sci. 12, no. 8: 5011-5030.

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