scholarly journals G-Protein coupled receptors: answers from simulations

2017 ◽  
Vol 13 ◽  
pp. 1071-1078 ◽  
Author(s):  
Timothy Clark
Keyword(s):  
Molecular Dynamics ◽  
Drug Design ◽  
G Protein ◽  
Experimental Situation ◽  
Md Simulations ◽  
G Protein Coupled Receptors ◽  
Computer Aided Drug Design ◽  
Computer Aided ◽  
Soft And Hardware ◽  
G Protein Coupled

Molecular-dynamics (MD) simulations are playing an increasingly important role in research into the modes of action of G-protein coupled receptors (GPCRs). In this field, MD simulations are unusually important as, because of the difficult experimental situation, they often offer the only opportunity to determine structural and mechanistic features in atomistic detail. Modern combinations of soft- and hardware have made MD simulations a powerful tool in GPCR research. This is important because GPCRs are targeted by approximately half of the drugs on the market, so that computer-aided drug design plays a major role in GPCR research.

Novel Insights into Biased Agonism at G Protein-Coupled Receptors and their Potential for Drug Design

2013 ◽  
Vol 19 (28) ◽  
pp. 5156-5166 ◽  
Author(s):  
Maria Marti-Solano ◽  
Ramon Guixa-Gonzalez ◽  
Ferran Sanz ◽  
Manuel Pastor ◽  
Jana Selent
Keyword(s):  
Drug Design ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Biased Agonism ◽  
G Protein Coupled

scholarly journals Peeking at G-protein-coupled receptors through the molecular dynamics keyhole

2019 ◽  
Vol 11 (6) ◽  
pp. 599-615 ◽  
Author(s):  
Giuseppe Deganutti ◽  
Stefano Moro ◽  
Christopher A Reynolds
Keyword(s):  
Molecular Dynamics ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

scholarly journals Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics Approaches: Impact on Rational Drug Design

2018 ◽  
Vol 9 ◽  
Author(s):  
Shaherin Basith ◽  
Minghua Cui ◽  
Stephani J. Y. Macalino ◽  
Jongmi Park ◽  
Nina A. B. Clavio ◽  
...  
Keyword(s):  
Drug Design ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Rational Drug Design ◽  
Rational Drug ◽  
G Protein Coupled

Polypharmacology – a challenge for current drug design approaches

2019 ◽  
Vol 6 (3) ◽  
pp. 19-23
Author(s):  
Sabina Podlewska ◽  
Rafał Kurczab
Keyword(s):  
Molecular Modeling ◽  
Side Effects ◽  
Drug Design ◽  
G Protein ◽  
Design Process ◽  
Serotonin Receptors ◽  
G Protein Coupled Receptors ◽  
Activity Profile ◽  
Activity Groups ◽  
G Protein Coupled

Drug design process faces many challenges, and the most important ones are connected with side effects. Finding compounds that possess affinity towards target of interest is relatively simple; however, an approach one disease-one target is now making space for the search of polypharmacological ligands, where activity towards several proteins is considered at one time. Such proteins are not always the target ones, but very often such panels include also anti-targets, interaction with which is not desired, due to the side effects that may occur upon such contact. In the study, we examined ligands of four G protein-coupled receptors, forming antipsychotic profile: dopamine receptor D2, serotonin receptors 5-HT2A, 5-HT2C (anti-target), and 5-HT6. Number of ligands belonging to particular activity groups, as well as the selected compound structures are examined in detail. Also compound similarity between sets of different activity groups is analysed, giving a picture of difficulty of constructing molecular modeling methodologies that can help in the search of compounds with desired activity profile.

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.

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