title: Modeling the structural communication in supramolecular complexes involving GPCRs.
abstract: This article describes a computational strategy aimed at studying the structural communication in G-Protein Coupled Receptors (GPCRs) and G proteins. The strategy relies on comparative Molecular Dynamics (MD) simulations and analyses of wild-type (i.e., reference state) vs. mutated (i.e., perturbed state), or free (i.e., reference state) vs. bound (i.e., perturbed state) forms of a GPCR or a G protein. Bound forms of a GPCR include complexes with small ligands and/or receptor dimers/oligomers, whereas bound forms of heterotrimeric GDP-bound G proteins concern the complex with a GPCR. The computational strategy includes structure prediction of a receptor monomer (in the absence of high-resolution structure), a receptor dimer/oligomer, and a receptor-G protein complex, which constitute the inputs of MD simulations. Finally, the analyses of the MD trajectories are instrumental in inferring the structural/dynamics differences between reference and perturbed states of a GPCR or a G protein. In this respect, focus will be put on the analysis of protein structure networks and communication paths.
authors.affiliation: Department of Chemistry, Dulbecco Telethon Institute (DTI), University of Modena and Reggio Emilia, Modena, Italy. fanelli@unimo.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
mesh_terms: D019295:Computational Biology / Q000379:methods*; D044385:GTP-Binding Protein alpha Subunits / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D011974:Receptors, LH / Q000737:chemistry
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D050505:Mutant Proteins; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH