Simulated Docking of the α2B Adrenergic Receptor with Agonistic and Antagonistic Ligands
Institution
Eastern Kentucky University
Faculty Advisor/ Mentor
Debra Bautista
Abstract
Alpha 2-Adrenergic Receptors (α2-ARs) belong to the superfamily of G-ProteinCoupled Receptors (GPCRs). In this study, the receptor of interest was the alpha 2b receptor. These receptors have been shown to play an integral role in cellular signaling. The alpha 2b receptor has been found to have control of lipolysis during exercise in adipose tissue. All GPCRs are predicted to share a common molecular architecture consisting of seven alpha helical transmembranes linked by alternating intracellular and extracellular loops. The extracellular receptor surface has been shown to be critical for ligand binding, and the intracellular surface is known to be involved in G-protein recognition and activation. The alpha 2b model was of interest because it is known to play an integral role in smooth muscle contraction. A model of the Antagonist alpha 2b AR was made by using Bovine Rhodopsin to facilitate rational drug design. Bovine Rhodopsin is used because it is the only known GPCR crystallized to date. Secondly, known antagonist ligands were used in docking simulations to the model to see if they interacted with the model as predicted by the literature. Results indicate that further refinement of the alpha 2b AR model is necessary.
Simulated Docking of the α2B Adrenergic Receptor with Agonistic and Antagonistic Ligands
Alpha 2-Adrenergic Receptors (α2-ARs) belong to the superfamily of G-ProteinCoupled Receptors (GPCRs). In this study, the receptor of interest was the alpha 2b receptor. These receptors have been shown to play an integral role in cellular signaling. The alpha 2b receptor has been found to have control of lipolysis during exercise in adipose tissue. All GPCRs are predicted to share a common molecular architecture consisting of seven alpha helical transmembranes linked by alternating intracellular and extracellular loops. The extracellular receptor surface has been shown to be critical for ligand binding, and the intracellular surface is known to be involved in G-protein recognition and activation. The alpha 2b model was of interest because it is known to play an integral role in smooth muscle contraction. A model of the Antagonist alpha 2b AR was made by using Bovine Rhodopsin to facilitate rational drug design. Bovine Rhodopsin is used because it is the only known GPCR crystallized to date. Secondly, known antagonist ligands were used in docking simulations to the model to see if they interacted with the model as predicted by the literature. Results indicate that further refinement of the alpha 2b AR model is necessary.