Homology models of the cannabinoid CB1 and CB2 receptors. A docking analysis study.
The 3D models of both CB1 and CB2 human receptors have been established by homology modeling using as template the X-ray structure of bovine Rhodopsin (code pdb: 1F88) a G-protein-coupled receptor (GPCR). A recursive approach comprising sequence alignment and model building was used to build both models, followed by the refinement of non-conserved regions. The cannabinoid system has been studied by means of docking techniques, using the 3D models of both CB1 and CB2 and well known reference inverse agonist/antagonist compounds. An approach based on the flexibility of the structures has been used to model the receptor-ligand complexes. The structural effects of ligand binding were studied and analyzed on the basis of hydrogen bond interactions, and binding energy calculations. Potential interaction sites of the receptor were determined from analysis of the difference accessible surface area (DASA) study of the protein with and without ligand.
Montero
Cristina
C
Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Campillo
Nuria Eugenia
NE
Goya
Pilar
P
Páez
Juan Antonio
JA
D003198:Computer Simulation; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2