Molecular dynamics simulation involved in expounding the activation of adrenoceptors by sympathetic nervous system signaling

Abstract

G-protein–coupled receptors are integral membrane proteins involved in signal transduction pathways, making them an appealing drug targets for a wide spectrum of diseases. The previous literature reports provide an evidence that catecholamine regulates metastasis by actuating the β2-adrenergic receptor (β-2AR). Molecular dynamics simulations were carried out for 1000 ns to understand the effect of the catecholamine on the human β-2AR. On comparing the apoprotein structure of β-2AR with that of catecholamine interacted β-2AR protein, a large change in structural assembly is observed in the helical regions which confirm the activation of β-2AR protein. The visualization of internal natural pathway of β-2AR protein structure gives us detailed information about deviation in TM helixes. The compactness of protein structure shows β-2AR protein interacting with epinephrine is much stable than β-2AR protein interacting with norepinephrine structure. The Gibbs free energy shows norepinephrine as a partial agonist whereas epinephrine as full agonist for β-2AR protein.