Ligand Pose Predictions for Human G Protein-Coupled Receptors: Insights from the Amber-Based Hybrid Molecular Mechanics/Coarse-Grained Approach

2020 ◽  
Vol 60 (10) ◽  
pp. 5103-5116 ◽  
Author(s):  
Jakob Schneider ◽  
Ksenia Korshunova ◽  
Zeineb Si Chaib ◽  
Alejandro Giorgetti ◽  
Mercedes Alfonso-Prieto ◽  
...  
Keyword(s):  
Molecular Mechanics ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Coarse Grained ◽  
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 Activation of G-protein coupled receptors is thermodynamically linked to lipid solvation

2020 ◽  
Author(s):  
Alison N. Leonard ◽  
Edward Lyman
Keyword(s):  
G Protein ◽  
Chemical Potential ◽  
Solvation Shell ◽  
G Protein Coupled Receptors ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Unsaturated Lipids ◽  
Bulk Membrane ◽  
Enthalpy And Entropy ◽  
G Protein Coupled

AbstractPreferential lipid solvation of the G-protein coupled A2A adenosine receptor (A2AR) is evaluated from 35 μsec of all-atom molecular dynamics simulation. A coarse-grained transition matrix algorithm is developed to overcome slow equilibration of the first solvation shell, obtaining statistically robust estimates of the free energy of solvation by different lipids for the receptor in different activation states. Results indicate preference for solvation by unsaturated chains, which favors the active receptor. A model for lipid-dependent GPCR activity is proposed in which the chemical potential of lipids in the bulk membrane modulates receptor activity. The enthalpy and entropy associated with moving saturated vs. unsaturated lipids from bulk to A2AR’s first solvation shell are compared. In the simulated mixture, saturated chains are disordered (i.e., obtain a favorable entropic contribution) when partitioning to the receptor surface, but this is outweighed by a favorable enthalpic contribution for unsaturated chains to occupy the first solvation shell.

Coarse-Grained Prediction of Peptide Binding to G-Protein Coupled Receptors

2017 ◽  
Vol 57 (3) ◽  
pp. 562-571 ◽  
Author(s):  
Bartholomé Delort ◽  
Pedro Renault ◽  
Landry Charlier ◽  
Florent Raussin ◽  
Jean Martinez ◽  
...  
Keyword(s):  
G Protein ◽  
Peptide Binding ◽  
G Protein Coupled Receptors ◽  
Coarse Grained ◽  
G Protein Coupled

scholarly journals Hybrid Molecular Mechanics/Coarse-Grained Simulations for Structural Prediction of G-Protein Coupled Receptor/Ligand Complexes

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47332 ◽  
Author(s):  
Michael Leguèbe ◽  
Chuong Nguyen ◽  
Luciana Capece ◽  
Zung Hoang ◽  
Alejandro Giorgetti ◽  
...  
Keyword(s):  
Molecular Mechanics ◽  
G Protein ◽  
Coarse Grained ◽  
G Protein Coupled Receptor ◽  
Receptor Ligand ◽  
Structural Prediction ◽  
Coarse Grained Simulations ◽  
G Protein Coupled
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