molecular dynamics of a biophysical model for -adrenergic and.pdfVIP

Journal of Molecular Graphics and Modelling 25 (2006) 396–409 /locate/JMGM Molecular dynamics of a biophysical model for b -adrenergic 2 and G protein-coupled receptor activation§ Lester A. Rubenstein a,, Randy J. Zauhar b, Richard G. Lanzara c,* a Department of Physiology and Biophysics, Mount Sinai School of Medicine, One Gustav Levy Place, New York, NY 10029, United States b Department of Chemistry and Biochemistry, The University of the Sciences in Philadelphia, 600 S. 43rd Street, Philadelphia, PA 19104, United States c Bio Balance, Inc. Pharmacology, 30 West 86th Street, New York, NY 10024, United States Received 14 December 2005; received in revised form 17 February 2006; accepted 21 February 2006 Available online 30 March 2006 Abstract This study analyzes 16 molecular dynamic simulations of a biophysical model for b2-adrenergic (B2AR) and G protein-coupled receptor (GPCR) activation. In this model, a highly conserved cysteine residue, C106 (C3.25 or CysIII:01), provides a free sulfhydryl or thiol group in an acid–base equilibrium between uncharged (RSH) and charged (RS) states that functions as an electrostatic molecular switch for receptor activation. The transition of C106 in the B2AR between acid and base states significantly c