Three-dimensional models of the CB1 and CB2 cannabinoid receptors were constructed by means of a molecular modeling procedure, using the X-ray structure of bovine rhodopsin as the initial template, and taking into account the available site-directed mutagenesis data. The cannabinoid system was studied by means of docking techniques. An analysis of the interaction of WIN55212-2 with both receptors showed that CB2/CB1 selectivity is mainly determined by the interaction in the CB2 with the nonconserved residues S3.31 and F5.46, whose importance was suggested by site-directed mutagenesis data. We also carried out an automated docking of several ligands into the CB2 model, using the AUTODOCK 3.0 program; the good correlation obtained between the estimated free energy binding and the experimental binding data confirmed our binding hypothesis and the reliability of the model.

Cannabinoid CB2/CB1 Selectivity. Receptor Modeling and Automated Docking Analysis

TUCCINARDI, TIZIANO;FERRARINI, PIER LUIGI;MANERA, CLEMENTINA;ORTORE, GABRIELLA MARIA PIA;SACCOMANNI, GIUSEPPE;MARTINELLI, ADRIANO
2006

Abstract

Three-dimensional models of the CB1 and CB2 cannabinoid receptors were constructed by means of a molecular modeling procedure, using the X-ray structure of bovine rhodopsin as the initial template, and taking into account the available site-directed mutagenesis data. The cannabinoid system was studied by means of docking techniques. An analysis of the interaction of WIN55212-2 with both receptors showed that CB2/CB1 selectivity is mainly determined by the interaction in the CB2 with the nonconserved residues S3.31 and F5.46, whose importance was suggested by site-directed mutagenesis data. We also carried out an automated docking of several ligands into the CB2 model, using the AUTODOCK 3.0 program; the good correlation obtained between the estimated free energy binding and the experimental binding data confirmed our binding hypothesis and the reliability of the model.
Tuccinardi, Tiziano; Ferrarini, PIER LUIGI; Manera, Clementina; Ortore, GABRIELLA MARIA PIA; Saccomanni, Giuseppe; Martinelli, Adriano
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/181079
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