title: Structure network analysis to gain insights into GPCR function.
abstract: G protein coupled receptors (GPCRs) are allosteric proteins whose functioning fundamentals are the communication between the two poles of the helix bundle. Protein structure network (PSN) analysis is one of the graph theory-based approaches currently used to investigate the structural communication in biomolecular systems. Information on system's dynamics can be provided by atomistic molecular dynamics (MD) simulations or coarse grained elastic network models paired with normal mode analysis (ENM-NMA). The present review article describes the application of PSN analysis to uncover the structural communication in G protein coupled receptors (GPCRs). Strategies to highlight changes in structural communication upon misfolding, dimerization and activation are described. Focus is put on the ENM-NMA-based strategy applied to the crystallographic structures of rhodopsin in its inactive (dark) and signalling active (meta II (MII)) states, highlighting changes in structure network and centrality of the retinal chromophore in differentiating the inactive and active states of the receptor.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy fanelli@unimo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Felline
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Raimondi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Seeber
mesh_terms: D056004:Molecular Dynamics Simulation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: G protein coupled receptors (GPCRs); elastic network model-normal mode analysis; molecular dynamics simulations; protein structure networks; structural communication