tailieunhanh - Báo cáo khoa học: The study of G-protein coupled receptor oligomerization with computational modeling and bioinformatics

To achieve a structural context for the analysis of G-protein coupled recep-tor (GPCR) oligomers, molecular modeling must be used to predict the corresponding interaction interfaces. The task is complicated by the paucity of detailed structural data at atomic resolution, and the large number of possible modes in which the bundles of seven transmembrane (TM) seg-ments of the interacting GPCR monomers can be packed together into dimers and⁄or higher-order oligomers. | iFEBS Journal MINIREVIEW The study of G-protein coupled receptor oligomerization with computational modeling and bioinformatics Marta Filizola1 and Harel Weinstein1 2 1 Department of Physiology and Biophysics WeillMedicalCollege of CornellUniversity NY USA 2 Institute for ComputationalBiomedicine ICB WeillMedicalCollege of CornellUniversity NY USA Keywords bioinformatics GPCRs interface molecular modeling oligomerization Correspondence M. Filizola Department of Physiology and Biophysics Box 75 WeillMedicalCollege of CornellUniversity 1300 York Avenue New York NY 10021 USA Fax 01 212 746 8690 Tel 01 212 746 6348 E-mail maf2037@ Received 16 February 2005 accepted 8 April 2005 doi To achieve a structural context for the analysis of G-protein coupled receptor GPCR oligomers molecular modeling must be used to predict the corresponding interaction interfaces. The task is complicated by the paucity of detailed structural data at atomic resolution and the large number of possible modes in which the bundles of seven transmembrane TM segments of the interacting GPCR monomers can be packed together into dimers and or higher-order oligomers. Approaches and tools offered by bioinformatics can be used to reduce the complexity of this task and combined with computational modeling can serve to yield testable predictions for the structural properties of oligomers. Most of the bioinformatics methods take advantage of the evolutionary relation that exists among GPCRs as expressed in their sequences and measurable in the common elements of their structural and functional features. These common elements are responsible for the presence of detectable patterns of motifs and correlated mutations evident from the alignment of the sequences of these complex biological systems. The decoding of these patterns in terms of structural and functional determinants can provide indications about the most likely interfaces of dimerization .