scholarly journals Influence of oligomerization on the dynamics of G-protein coupled receptors as assessed by normal mode analysis

2008 ◽  
Vol 71 (2) ◽  
pp. 575-586 ◽  
Author(s):  
Masha Y. Niv ◽  
Marta Filizola
Keyword(s):  
G Protein ◽  
Normal Mode ◽  
Normal Mode Analysis ◽  
G Protein Coupled Receptors ◽  
Mode Analysis ◽  
G Protein Coupled

Structure network analysis to gain insights into GPCR function

2016 ◽  
Vol 44 (2) ◽  
pp. 613-618 ◽  
Author(s):  
Francesca Fanelli ◽  
Angelo Felline ◽  
Francesco Raimondi ◽  
Michele Seeber
Keyword(s):  
G Protein ◽  
Normal Mode Analysis ◽  
Network Models ◽  
Md Simulations ◽  
G Protein Coupled Receptors ◽  
Coarse Grained ◽  
Mode Analysis ◽  
Biomolecular Systems ◽  
Retinal Chromophore ◽  
G Protein Coupled

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.

scholarly journals Dynamical Correlations Reveal Allosteric Sites in G Protein-Coupled Receptors

2020 ◽  
Vol 22 (1) ◽  
pp. 187
Author(s):  
Pedro Renault ◽  
Jesús Giraldo
Keyword(s):  
G Protein ◽  
Conformational Changes ◽  
Drug Targets ◽  
Normal Mode Analysis ◽  
G Protein Coupled Receptors ◽  
Mode Analysis ◽  
Allosteric Sites ◽  
Basic Hypothesis ◽  
Dynamics Simulations ◽  
G Protein Coupled

G protein-coupled Receptors (GPCRs) play a central role in many physiological processes and, consequently, constitute important drug targets. In particular, the search for allosteric drugs has recently drawn attention, since they could be more selective and lead to fewer side effects. Accordingly, computational tools have been used to estimate the druggability of allosteric sites in these receptors. In spite of many successful results, the problem is still challenging, particularly the prediction of hydrophobic sites in the interface between the protein and the membrane. In this work, we propose a complementary approach, based on dynamical correlations. Our basic hypothesis was that allosteric sites are strongly coupled to regions of the receptor that undergo important conformational changes upon activation. Therefore, using ensembles of experimental structures, normal mode analysis and molecular dynamics simulations we calculated correlations between internal fluctuations of different sites and a collective variable describing the activation state of the receptor. Then, we ranked the sites based on the strength of their coupling to the collective dynamics. In the β2 adrenergic (β2AR), glucagon (GCGR) and M2 muscarinic receptors, this procedure allowed us to correctly identify known allosteric sites, suggesting it has predictive value. Our results indicate that this dynamics-based approach can be a complementary tool to the existing toolbox to characterize allosteric sites in GPCRs.

Sign in / Sign up

Export Citation Format

Share Document