title: Investigation of the structure requirement for 5-HT₆ binding affinity of arylsulfonyl derivatives: a computational study.
abstract: 5-HT(6) receptor has been implicated in a series of diseases including anxiety, depression, schizophrenia and cognitive dysfunctions. 5-HT(6) 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-HT(6) 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(2) (ncv), 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(2) (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-HT(6) ligands.
authors.affiliation: Department of Materials Science and Chemical Engineering, Dalian University of Technology, Dalian 116023, Liaoning, China; E-Mails:  dluthm@yeah.net  (M.H.);  lihanqing00@gmail.com  (H.L.);  zswei@dlut.edu.cn  (S.Z.).
authors.forename: Ming
authors.initials: M
authors.lastname: Hao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Hanqing
authors.initials: H
authors.lastname: Li
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D008024:Ligands; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor