scholarly journals G Protein-Coupled Receptors Self-Assemble in Dynamics Simulations of Model Bilayers

2007 ◽  
Vol 129 (33) ◽  
pp. 10126-10132 ◽  
Author(s):  
Xavier Periole ◽  
Thomas Huber ◽  
Siewert-Jan Marrink ◽  
Thomas P. Sakmar
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Dynamics Simulations ◽  
G Protein Coupled

scholarly journals Development of OPLS-AA/M Parameters for Simulations of G Protein-Coupled Receptors and Other Membrane Proteins

2022 ◽  
Author(s):  
Michael J. Robertson ◽  
Georgios Skiniotis
Keyword(s):  
Membrane Proteins ◽  
Force Field ◽  
G Protein ◽  
Drug Targets ◽  
G Protein Coupled Receptors ◽  
Dynamic Nature ◽  
Post Translational Modifications ◽  
Dynamics Simulations ◽  
High Level ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) and other membrane proteins are valuable drug targets, and their dynamic nature makes them attractive systems for study with molecular dynamics simulations and free energy approaches. Here, we report the development, implementation, and validation of OPLS-AA/M force field parameters to enable simulations of these systems. These efforts include the introduction of post-translational modifications including lipidations and phosphorylation. We also modify previously reported parameters for lipids to be more consistent with the OPLS-AA force field standard and extend their coverage. These new parameters are validated on a variety of test systems, with the results compared to high-level quantum mechanics calculations, experimental data, and simulations with CHARMM36m where relevant. The results demonstrate that the new parameters reliably reproduce the behavior of membrane protein systems.

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.

scholarly journals Insights into G-Protein Coupled Receptors Activation from All-Atom Molecular Dynamics Simulations

2010 ◽  
Vol 98 (3) ◽  
pp. 419a-420a
Author(s):  
Stefano Vanni ◽  
Marilisa Neri ◽  
Ivano Tavernelli ◽  
Ursula Rothlisberger
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Dynamics Simulations ◽  
G Protein Coupled
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