3D-QSAR studies on cannabinoid CB1 receptor agonists: G-protein activation as biological data

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Salo, Savinainen, Parkkari, Nevalainen, Lahtela-Kakkonen, Gynther, Laitinen, Järvinen, Poso
Publiceringsår: 2006
Tidskrift: Journal of Medicinal Chemistry
Tidskriftsakronym: J Med Chem
Volym: 49
Nummer: 2
Artikelns första sida, sidnummer: 554
Artikelns sista sida, sidnummer: 566
ISSN: 0022-2623
eISSN: 1520-4804


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.

Senast uppdaterad 2020-30-05 vid 03:56