Simulations of Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular Dynamics英文.pdfVIP

Article /biochemistry Terms of Use Simulations of Biased Agonists in the β 2 Adrenergic Receptor with Accelerated Molecular Dynamics Irina G. Tikhonova,*,§ Balaji Selvam,§ Anthony Ivetac,△ Je ff Wereszczynski,# and J. Andrew McCammon△,▽,□,○ §Molecular Therapeutics, School of Pharmacy, Medical Biology Centre, Queen’s University, Belfast BT9 7BL, Northern Ireland, United Kingdom △Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0365, United States #Department of Physics, Illinois Institute of Technology, Chicago, Illinois 60616-3893, United States ▽Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California 92093-0365, United States □Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0365, United States ○Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0365, United States S *Supporting Information ABSTRACT: The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signaling pathway a GPCR promotes intracellular signals though β-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signaling through the G protein and β-arrestin. Here we report on the dynamics of the β2 adrenergic receptor bound to the β-arresti