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Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics

An increasingly comprehension of the folding intermediate states of DNA G-quadruplexes (G4s) is currently an important scientific challenge, especially for the human telomeric (h-tel) G4s-forming sequences, characterized by a highly polymorphic nature. Despite the G-triplex conformation was proposed...

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Autores principales: Rocca, Roberta, Palazzesi, Ferruccio, Amato, Jussara, Costa, Giosuè, Ortuso, Francesco, Pagano, Bruno, Randazzo, Antonio, Novellino, Ettore, Alcaro, Stefano, Moraca, Federica, Artese, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035250/
https://www.ncbi.nlm.nih.gov/pubmed/32081872
http://dx.doi.org/10.1038/s41598-020-59774-x
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author Rocca, Roberta
Palazzesi, Ferruccio
Amato, Jussara
Costa, Giosuè
Ortuso, Francesco
Pagano, Bruno
Randazzo, Antonio
Novellino, Ettore
Alcaro, Stefano
Moraca, Federica
Artese, Anna
author_facet Rocca, Roberta
Palazzesi, Ferruccio
Amato, Jussara
Costa, Giosuè
Ortuso, Francesco
Pagano, Bruno
Randazzo, Antonio
Novellino, Ettore
Alcaro, Stefano
Moraca, Federica
Artese, Anna
author_sort Rocca, Roberta
collection PubMed
description An increasingly comprehension of the folding intermediate states of DNA G-quadruplexes (G4s) is currently an important scientific challenge, especially for the human telomeric (h-tel) G4s-forming sequences, characterized by a highly polymorphic nature. Despite the G-triplex conformation was proposed as one of the possible folding intermediates for the antiparallel and hybrid h-tel G4s, for the parallel h-tel topology with an all-anti guanine orientation, a vertical strand-slippage involving the G-triplets was proposed in previous works through microseconds-long standard molecular dynamics simulations (MDs). Here, in order to get further insights into the vertical strand-slippage and the folding intermediate states of the parallel h-tel G4s, we have carried out a Well-Tempered Metadynamics simulation (WT-MetaD), which allowed us to retrieve an ensemble of six G4s having two/G-tetrad conformations derived by the G-triplets vertical slippage. The insights highlighted in this work are aimed at rationalizing the mechanistic characterisation of the parallel h-tel G4 folding process.
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spelling pubmed-70352502020-02-28 Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics Rocca, Roberta Palazzesi, Ferruccio Amato, Jussara Costa, Giosuè Ortuso, Francesco Pagano, Bruno Randazzo, Antonio Novellino, Ettore Alcaro, Stefano Moraca, Federica Artese, Anna Sci Rep Article An increasingly comprehension of the folding intermediate states of DNA G-quadruplexes (G4s) is currently an important scientific challenge, especially for the human telomeric (h-tel) G4s-forming sequences, characterized by a highly polymorphic nature. Despite the G-triplex conformation was proposed as one of the possible folding intermediates for the antiparallel and hybrid h-tel G4s, for the parallel h-tel topology with an all-anti guanine orientation, a vertical strand-slippage involving the G-triplets was proposed in previous works through microseconds-long standard molecular dynamics simulations (MDs). Here, in order to get further insights into the vertical strand-slippage and the folding intermediate states of the parallel h-tel G4s, we have carried out a Well-Tempered Metadynamics simulation (WT-MetaD), which allowed us to retrieve an ensemble of six G4s having two/G-tetrad conformations derived by the G-triplets vertical slippage. The insights highlighted in this work are aimed at rationalizing the mechanistic characterisation of the parallel h-tel G4 folding process. Nature Publishing Group UK 2020-02-21 /pmc/articles/PMC7035250/ /pubmed/32081872 http://dx.doi.org/10.1038/s41598-020-59774-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Rocca, Roberta
Palazzesi, Ferruccio
Amato, Jussara
Costa, Giosuè
Ortuso, Francesco
Pagano, Bruno
Randazzo, Antonio
Novellino, Ettore
Alcaro, Stefano
Moraca, Federica
Artese, Anna
Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics
title Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics
title_full Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics
title_fullStr Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics
title_full_unstemmed Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics
title_short Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics
title_sort folding intermediate states of the parallel human telomeric g-quadruplex dna explored using well-tempered metadynamics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035250/
https://www.ncbi.nlm.nih.gov/pubmed/32081872
http://dx.doi.org/10.1038/s41598-020-59774-x
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