Computer-Aided Identification of Ligands for GPCR Anti-Obesity Targets

Many orphan G-protein-coupled receptors (GPCR) have emerged as potential obesity targets. The authors are interested in the computer-aided discovery and development of small molecule anti-obesity agents targeting GPCR. Computational modeling studies have mainly been conducted on ghrelin receptor (GHS-R), melanocortin 4-receptor (MC4R), melanin-concentrating hormone 1 receptor (MCH1R) and cannabinoid 1 receptor (CB1R) in recent publications. Here, a homology modeling strategy for these receptors will be introduced, and the key structural features of their active and inactive conformations will be reviewed. In addition, the authors describe the uses of virtual screening methods to identify novel antagonists of MCH1R and CB1R, which provide valuable examples of the computer-aided design and structural optimization of GPCR ligands.