A computational study on cannabinoid receptors and potentbioactive cannabinoid ligands: homology modeling, docking,de novo drug design and molecular dynamics analysis

摘要

When X-ray structure of a ligand-bound receptoris not available, homology models of the protein of interestcan be used to obtain the ligand-binding cavities. The stero-electronic properties of these cavities are directly related tothe performed molecular model coordinates. Thus, the useof different template structures for homology may result invariation of ligand-binding modes. We have recently reportedthe MD simulations of a potent CB ligand at bovine rhodop-sin-based CB 1 and CB2 receptors (Durdagi et al., BioorgMed Chem 16:7377-7387, 2008). In this present study, ahomology modeling study based on the 02-adrenergic recep-tor for both CB I and CB2 receptors was performed, andthe results were compared with rhodopsin-based models. Inaddition, the role of membrane bilayers to the adopted con-formations of potent AMG3 CB ligand has been analyzedfor receptor-free and membrane-associated receptor systems.