Network analysis to uncover the structural communication in GPCRs

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). This 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 mutations, 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 signaling active (Meta II (MII)) states, highlighting clear changes in the protein structure network and the centrality of the retinal chromophore in differentiating the inactive and active states of the receptor.