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Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations

Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. In o...

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Detalles Bibliográficos
Autores principales: Gentile, Francesco, Deriu, Marco A., Licandro, Ginevra, Prunotto, Alessio, Danani, Andrea, Tuszynski, Jack A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272798/
https://www.ncbi.nlm.nih.gov/pubmed/26007168
http://dx.doi.org/10.3390/molecules20058316
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author Gentile, Francesco
Deriu, Marco A.
Licandro, Ginevra
Prunotto, Alessio
Danani, Andrea
Tuszynski, Jack A.
author_facet Gentile, Francesco
Deriu, Marco A.
Licandro, Ginevra
Prunotto, Alessio
Danani, Andrea
Tuszynski, Jack A.
author_sort Gentile, Francesco
collection PubMed
description Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. In order to provide new indications for the design of Toll-Like Receptor 7 (TLR7)-targeting drugs, the mechanism of interaction between the TLR7 and two important classes of agonists (imidazoquinoline and adenine derivatives) was investigated through docking and Molecular Dynamics simulations. To perform the computational analysis, a new model for the dimeric form of the receptors was necessary and therefore created. Qualitative and quantitative differences between agonists and inactive compounds were determined. The in silico results were compared with previous experimental observations and employed to define the ligand binding mechanism of TLR7.
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spelling pubmed-62727982019-01-07 Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations Gentile, Francesco Deriu, Marco A. Licandro, Ginevra Prunotto, Alessio Danani, Andrea Tuszynski, Jack A. Molecules Article Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. In order to provide new indications for the design of Toll-Like Receptor 7 (TLR7)-targeting drugs, the mechanism of interaction between the TLR7 and two important classes of agonists (imidazoquinoline and adenine derivatives) was investigated through docking and Molecular Dynamics simulations. To perform the computational analysis, a new model for the dimeric form of the receptors was necessary and therefore created. Qualitative and quantitative differences between agonists and inactive compounds were determined. The in silico results were compared with previous experimental observations and employed to define the ligand binding mechanism of TLR7. MDPI 2015-05-08 /pmc/articles/PMC6272798/ /pubmed/26007168 http://dx.doi.org/10.3390/molecules20058316 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gentile, Francesco
Deriu, Marco A.
Licandro, Ginevra
Prunotto, Alessio
Danani, Andrea
Tuszynski, Jack A.
Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations
title Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations
title_full Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations
title_fullStr Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations
title_full_unstemmed Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations
title_short Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations
title_sort structure based modeling of small molecules binding to the tlr7 by atomistic level simulations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272798/
https://www.ncbi.nlm.nih.gov/pubmed/26007168
http://dx.doi.org/10.3390/molecules20058316
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