Molecular dynamics simulation involved in expounding the activation of adrenoceptors by sympathetic nervous system signa
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ORIGINAL RESEARCH
Molecular dynamics simulation involved in expounding the activation of adrenoceptors by sympathetic nervous system signaling Rahul Suresh 1 & Vijayakumar Subramaniam 2 Received: 31 January 2020 / Accepted: 30 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords SNS signaling . GPCRs . Catecholamine . Adregenic receptors . MD simulation
Abbreviations GPCRs G-protein coupled receptors SNS Sympathetic nervous system MD Molecular dynamics β-2AR β2-adrenergic receptor TM Transmembrane CNS Central nervous system RMSD Root mean square deviation RMSF Root mean square fluctuation Rg Radius of gyration SASA Solvent accessible surface area FEL Free energy landscape
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11224-020-01553-5) contains supplementary material, which is available to authorized users. * Vijayakumar Subramaniam [email protected] 1
Department of Physics, Bharathiar University, Coimbatore, India
2
Department of Medical Physics, Bharathiar University, Coimbatore, India
Introduction G-protein–coupled receptors (GPCRs) are one of the best diverse cellular signalling systems, involved in the communication between interior and exterior of cells regulating cell activity and mediating critical physiological function [1–3]. Hence, GPCR is involved in several major disease areas including metabolic, cardiovascular psychiatric, cancer and neurodegenerative diseases [4, 5]. GPCRs moderate cellular responses to a variety of physical or chemical stimuli, such as neurotransmitters and hormones, as well as photons and are associated in numerous pathological (i.e. cell migration, vision, inflammatory response, cancer, platelet aggregation and CNS diseases) and physiological processes, thus representing the most druggable class of proteins [6, 7]. Indeed, 30–50% of the total drugs are targeted towards GPCR proteins either for activation (by agonist dru
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