Comparative molecular dynamics study of the seven-helix bundle arrangement of G-protein coupled receptors

A comparative molecular dynamics study has been performed on the seven-helix bundle arrangement of seven G-protein coupled receptors (GPCRs). They are hamster alpha(1B)-, human alpha(2)-, beta(2)-adrenergic, human D-2-dopaminergic, human 5-HT1A-serotoninergic, human ml-muscarinic receptors and bovine rhodopsin. Starting from a rhodopsin-like input structure and a bacteriorhodopsin-like input structure, a similar arrangement of the averaged helix bundles was obtained. This may be due to the topography of some fundamental polar positions in both the input structures which is substantially the same and dictates, through the establishment of similar H-bonding networks, the helix-helix packing. By comparing the averaged structures and the packing interaction parameters obtained for the GPCRs considered with that of bacteriorhodopsin, we observe that the GPCRs share a similar packing arrangement of their transmembrane helix bundles which differs from that of bacteriorhodopsin. The results obtained from the quantitative and comparative molecular modelling of the GPCRs constitute an important preliminary step in a general understanding of both structure-function and structure activity-selectivity relationships in these proteins, at the molecular level.