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Molecular Dynamics Simulations Reveal an Interplay between SHAPE Reagent Binding and RNA Flexibility
[Image: see text] The function of RNA molecules usually depends on their overall fold and on the presence of specific structural motifs. Chemical probing methods are routinely used in combination with nearest-neighbor models to determine RNA secondary structure. Among the available methods, SHAPE is...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830694/ https://www.ncbi.nlm.nih.gov/pubmed/29265824 http://dx.doi.org/10.1021/acs.jpclett.7b02921 |
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author | Mlýnský, Vojtěch Bussi, Giovanni |
author_facet | Mlýnský, Vojtěch Bussi, Giovanni |
author_sort | Mlýnský, Vojtěch |
collection | PubMed |
description | [Image: see text] The function of RNA molecules usually depends on their overall fold and on the presence of specific structural motifs. Chemical probing methods are routinely used in combination with nearest-neighbor models to determine RNA secondary structure. Among the available methods, SHAPE is relevant due to its capability to probe all RNA nucleotides and the possibility to be used in vivo. However, the structural determinants for SHAPE reactivity and its mechanism of reaction are still unclear. Here molecular dynamics simulations and enhanced sampling techniques are used to predict the accessibility of nucleotide analogs and larger RNA structural motifs to SHAPE reagents. We show that local RNA reconformations are crucial in allowing reagents to reach the 2′-OH group of a particular nucleotide and that sugar pucker is a major structural factor influencing SHAPE reactivity. |
format | Online Article Text |
id | pubmed-5830694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-58306942018-03-02 Molecular Dynamics Simulations Reveal an Interplay between SHAPE Reagent Binding and RNA Flexibility Mlýnský, Vojtěch Bussi, Giovanni J Phys Chem Lett [Image: see text] The function of RNA molecules usually depends on their overall fold and on the presence of specific structural motifs. Chemical probing methods are routinely used in combination with nearest-neighbor models to determine RNA secondary structure. Among the available methods, SHAPE is relevant due to its capability to probe all RNA nucleotides and the possibility to be used in vivo. However, the structural determinants for SHAPE reactivity and its mechanism of reaction are still unclear. Here molecular dynamics simulations and enhanced sampling techniques are used to predict the accessibility of nucleotide analogs and larger RNA structural motifs to SHAPE reagents. We show that local RNA reconformations are crucial in allowing reagents to reach the 2′-OH group of a particular nucleotide and that sugar pucker is a major structural factor influencing SHAPE reactivity. American Chemical Society 2017-12-21 2018-01-18 /pmc/articles/PMC5830694/ /pubmed/29265824 http://dx.doi.org/10.1021/acs.jpclett.7b02921 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Mlýnský, Vojtěch Bussi, Giovanni Molecular Dynamics Simulations Reveal an Interplay between SHAPE Reagent Binding and RNA Flexibility |
title | Molecular Dynamics Simulations Reveal an Interplay
between SHAPE Reagent Binding and RNA Flexibility |
title_full | Molecular Dynamics Simulations Reveal an Interplay
between SHAPE Reagent Binding and RNA Flexibility |
title_fullStr | Molecular Dynamics Simulations Reveal an Interplay
between SHAPE Reagent Binding and RNA Flexibility |
title_full_unstemmed | Molecular Dynamics Simulations Reveal an Interplay
between SHAPE Reagent Binding and RNA Flexibility |
title_short | Molecular Dynamics Simulations Reveal an Interplay
between SHAPE Reagent Binding and RNA Flexibility |
title_sort | molecular dynamics simulations reveal an interplay
between shape reagent binding and rna flexibility |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830694/ https://www.ncbi.nlm.nih.gov/pubmed/29265824 http://dx.doi.org/10.1021/acs.jpclett.7b02921 |
work_keys_str_mv | AT mlynskyvojtech moleculardynamicssimulationsrevealaninterplaybetweenshapereagentbindingandrnaflexibility AT bussigiovanni moleculardynamicssimulationsrevealaninterplaybetweenshapereagentbindingandrnaflexibility |