title: 3D-QSAR studies on cannabinoid CB1 receptor agonists: G-protein activation as biological data.
abstract: G-protein activation via the CB1 receptor was determined for a group of various CB1 ligands and utilized as biological activity data in subsequent CoMFA and CoMSIA studies. Both manual techniques and automated docking at CB1 receptor models were used to obtain a common alignment of endocannabinoid and classical cannabinoid derivatives. In the final alignment models, the endocannabinoid headgroup occupies a unique region distinct from the classical cannabinoid structures, supporting the hypothesis that these structurally diverse molecules overlap only partially within the receptor binding site. Both CoMFA and CoMSIA produce statistically significant models based on the manual alignment and a docking alignment at one receptor conformer. Leave-half-out cross-validation and progressive scrambling were successfully used in assessing the predictivity of the QSAR models.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, FIN-70211 Kuopio, Finland. outi.salo@uku.fi
authors.forename: Outi M H
authors.initials: OM
authors.lastname: Salo
authors.forename: Juha R
authors.initials: JR
authors.lastname: Savinainen
authors.forename: Teija
authors.initials: T
authors.lastname: Parkkari
authors.forename: Tapio
authors.initials: T
authors.lastname: Nevalainen
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
authors.forename: Jukka
authors.initials: J
authors.lastname: Gynther
authors.forename: Jarmo T
authors.initials: JT
authors.lastname: Laitinen
authors.forename: Tomi
authors.initials: T
authors.lastname: Järvinen
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
mesh_terms: D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000737:chemistry* / Q000494:pharmacology; D002531:Cerebellum / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000819:agonists* / Q000737:chemistry*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000737:chemistry*
chemical_list: D063385:Cannabinoid Receptor Modulators; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D019204:GTP-Binding Proteins