Modeling and Simulation Studies of Human beta 3 Adrenergic Receptor and its Interactions with Agonists

beta 3 adrenergic receptor (beta 3AR) is known to mediate various pharmacological and physiological effects such as thermogenesis in brown adipocytes, lipolysis in white adipocytes, glucose homeostasis and intestinal smooth muscle relaxation. Several efforts have been made in this field to understand their function and regulation in different human tissues and they have emerged as potential attractive targets in drug discovery for the treatment of diabetes, depression, obesity etc. Although the crystal structures of Bovine Rhodopsin and beta 2 adrenergic receptor have been resolved, to date there is no three dimensional structural information on beta 3AR. Our aim in this study was to model 3D structure of beta 3AR by various molecular modeling and simulation techniques. In this paper, we describe a refined predicted model of beta 3AR using different algorithms for structure prediction. The structural refinement and minimization of the generated 3D model of beta 3AR were done by Schrodinger suite 9.1. Docking studies of beta 3AR model with the known agonists enabled us to identify specific residues, viz, Asp 117, Ser 208, Ser 209, Ser 212, Arg 315, Asn 332, within the beta 3AR binding pocket, which might play an important role in ligand binding. Receptor ligand interaction studies clearly indicated that these five residues showed strong hydrogen bonding interactions with the ligands. The results have been correlated with the experimental data available. The predicted ligand binding interactions and the simulation studies validate the methods used to predict the 3D-structure.