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Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands
CC Chemokine receptor 5 (CCR5), a member of the Superfamily of G Protein-Coupled Receptors (GPCRs), is an important effector in multiple physiopathological processes such as inflammatory and infectious entities, including central nervous system neuroinflammatory diseases such as Alzheimer’s disease,...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576088/ https://www.ncbi.nlm.nih.gov/pubmed/36251708 http://dx.doi.org/10.1371/journal.pone.0275269 |
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author | Goode-Romero, Guillermo Dominguez, Laura |
author_facet | Goode-Romero, Guillermo Dominguez, Laura |
author_sort | Goode-Romero, Guillermo |
collection | PubMed |
description | CC Chemokine receptor 5 (CCR5), a member of the Superfamily of G Protein-Coupled Receptors (GPCRs), is an important effector in multiple physiopathological processes such as inflammatory and infectious entities, including central nervous system neuroinflammatory diseases such as Alzheimer’s disease, recovery from nervous injuries, and in the HIV-AIDS infective processes. Thus, CCR5 is an attractive target for pharmacological modulation. Since maraviroc was described as a CCR5 ligand that modifies the HIV-AIDS progression, multiple efforts have been developed to describe the functionality of the receptor. In this work, we characterized key structural features of the CCR5 receptor employing extensive atomistic molecular dynamics (MD) in its apo form and in complex with an endogenous agonist, the chemokine CCL5/RANTES, an HIV entry inhibitor, the partial inverse agonist maraviroc, and the experimental antagonists Compound 21 and 34, aiming to elucidate the structural features and mechanistic processes that constitute its functional states, contributing with structural details and a general understanding of this relevant system. |
format | Online Article Text |
id | pubmed-9576088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-95760882022-10-18 Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands Goode-Romero, Guillermo Dominguez, Laura PLoS One Research Article CC Chemokine receptor 5 (CCR5), a member of the Superfamily of G Protein-Coupled Receptors (GPCRs), is an important effector in multiple physiopathological processes such as inflammatory and infectious entities, including central nervous system neuroinflammatory diseases such as Alzheimer’s disease, recovery from nervous injuries, and in the HIV-AIDS infective processes. Thus, CCR5 is an attractive target for pharmacological modulation. Since maraviroc was described as a CCR5 ligand that modifies the HIV-AIDS progression, multiple efforts have been developed to describe the functionality of the receptor. In this work, we characterized key structural features of the CCR5 receptor employing extensive atomistic molecular dynamics (MD) in its apo form and in complex with an endogenous agonist, the chemokine CCL5/RANTES, an HIV entry inhibitor, the partial inverse agonist maraviroc, and the experimental antagonists Compound 21 and 34, aiming to elucidate the structural features and mechanistic processes that constitute its functional states, contributing with structural details and a general understanding of this relevant system. Public Library of Science 2022-10-17 /pmc/articles/PMC9576088/ /pubmed/36251708 http://dx.doi.org/10.1371/journal.pone.0275269 Text en © 2022 Goode-Romero, Dominguez https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Goode-Romero, Guillermo Dominguez, Laura Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands |
title | Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands |
title_full | Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands |
title_fullStr | Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands |
title_full_unstemmed | Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands |
title_short | Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands |
title_sort | computational study of the structural ensemble of cc chemokine receptor type 5 (ccr5) and its interactions with different ligands |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576088/ https://www.ncbi.nlm.nih.gov/pubmed/36251708 http://dx.doi.org/10.1371/journal.pone.0275269 |
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