caa a22 4500 467938601 CHVBK 20180406153005.0 cr unu---uuuuu 170328e20060801xx s 000 0 eng 10.1007/s10822-006-9053-3 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9053-3 Dynamic models of G-protein coupled receptor dimers: indications of asymmetry in the rhodopsin dimer from molecular dynamics simulations in a POPC bilayer [Elektronische Daten] [Marta Filizola, Simon Wang, Harel Weinstein] Based on the growing evidence that G-protein coupled receptors (GPCRs) form homo- and hetero-oligomers, models of GPCR signaling are now considering macromolecular assemblies rather than monomers, with the homo-dimer regarded as the minimal oligomeric arrangement required for functional coupling to the G-protein. The dynamic mechanisms of such signaling assemblies are unknown. To gain some insight into properties of GPCR dimers that may be relevant to functional mechanisms, we study their current structural prototype, rhodopsin. We have carried out nanosecond time-scale molecular dynamics (MD) simulations of a rhodopsin dimer and compared the results to the monomer simulated in the same type of bilayer membrane model composed of an equilibrated unit cell of hydrated palmitoyl-oleoyl-phosphatidyl choline (POPC). The dynamic representation of the homo-dimer reveals the location of structural changes in several regions of the monomeric subunits. These changes appear to be more pronounced at the dimerization interface that had been shown to be involved in the activation process [Proc Natl Acad Sci USA 102:17495, 2005]. The results are consistent with a model of GPCR activation that involves allosteric modulation through a single GPCR subunit per dimer. Springer Science+Business Media B.V., 2006 GPCRs nationallicence Dimerization nationallicence Allosteric mechanism nationallicence Dynamic mechanisms nationallicence Membrane bilayer nationallicence Essential dynamics nationallicence GROMACS nationallicence Filizola Marta Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1300 York Ave, 10021, New York, NY, USA aut Wang Simon Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1300 York Ave, 10021, New York, NY, USA aut Weinstein Harel Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1300 York Ave, 10021, New York, NY, USA aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/7-8(2006-08-01), 405-416 0920-654X 20:7-8<405 2006 20 10822 https://doi.org/10.1007/s10822-006-9053-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9053-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Filizola Marta Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1300 York Ave, 10021, New York, NY, USA aut NATIONALLICENCE 700 1- Wang Simon Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1300 York Ave, 10021, New York, NY, USA aut NATIONALLICENCE 700 1- Weinstein Harel Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1300 York Ave, 10021, New York, NY, USA aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/7-8(2006-08-01), 405-416 0920-654X 20:7-8<405 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer