This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Exploration of the structural features of G-protein coupled receptor (GPCR) dimerization/oligomerization is at its very beginning. Both computation and experiment seek to reveal the basis of protein interactions in GPCR dimers, and the dynamic properties that may relate to the functional mechanisms. Inferences from a recent atomic-force microscopy map of rhodopsin molecules in their native mouse disk membranes (Liang et al., J. Biol. Chem. 2003, 278:21655-21662) suggest that rhodopsin is organized into two-dimensional arrays of dimers, with the transmembrane (TM) helices 4 and 5 involved in intradimeric contact. Our plan is to carry out a detailed molecular dynamics (MD) simulation of the recently proposed molecular model of the TM4,5-TM4,5 rhodopsin dimer within a large unit cell (a=160 b= 124 and c= 98 ) of a hydrated patch of palmitoyl-oleoyl-phosphatidyl choline (POPC) lipid bilayer membrane containing 20 16 2 POPC molecules. Results from this simulation will be compared with those from parallel calculations performed on the rhodopsin monomer with the goal of identifying domains of high flexibility in the nanosecond range that may be functionally important with regard to oligomerization. The inferences concerning structural relaxation of the dimeric system within a meaningful explicit representation of the molecular membrane environment are generalizable to other GPCRs in the same family, for which only homology models are available.
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