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Integrated NMR/Molecular Dynamics Determination of the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop
[Image: see text] Both experimental and theoretical structure determinations of RNAs have remained challenging due to the intrinsic dynamics of RNAs. We report here an integrated nuclear magnetic resonance/molecular dynamics (NMR/MD) structure determination approach to describe the dynamic structure...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401711/ https://www.ncbi.nlm.nih.gov/pubmed/37479220 http://dx.doi.org/10.1021/jacs.3c03578 |
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author | Oxenfarth, Andreas Kümmerer, Felix Bottaro, Sandro Schnieders, Robbin Pinter, György Jonker, Hendrik R. A. Fürtig, Boris Richter, Christian Blackledge, Martin Lindorff-Larsen, Kresten Schwalbe, Harald |
author_facet | Oxenfarth, Andreas Kümmerer, Felix Bottaro, Sandro Schnieders, Robbin Pinter, György Jonker, Hendrik R. A. Fürtig, Boris Richter, Christian Blackledge, Martin Lindorff-Larsen, Kresten Schwalbe, Harald |
author_sort | Oxenfarth, Andreas |
collection | PubMed |
description | [Image: see text] Both experimental and theoretical structure determinations of RNAs have remained challenging due to the intrinsic dynamics of RNAs. We report here an integrated nuclear magnetic resonance/molecular dynamics (NMR/MD) structure determination approach to describe the dynamic structure of the CUUG tetraloop. We show that the tetraloop undergoes substantial dynamics, leading to averaging of the experimental data. These dynamics are particularly linked to the temperature-dependent presence of a hydrogen bond within the tetraloop. Interpreting the NMR data by a single structure represents the low-temperature structure well but fails to capture all conformational states occurring at a higher temperature. We integrate MD simulations, starting from structures of CUUG tetraloops within the Protein Data Bank, with an extensive set of NMR data, and provide a structural ensemble that describes the dynamic nature of the tetraloop and the experimental NMR data well. We thus show that one of the most stable and frequently found RNA tetraloops displays substantial dynamics, warranting such an integrated structural approach. |
format | Online Article Text |
id | pubmed-10401711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-104017112023-08-05 Integrated NMR/Molecular Dynamics Determination of the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop Oxenfarth, Andreas Kümmerer, Felix Bottaro, Sandro Schnieders, Robbin Pinter, György Jonker, Hendrik R. A. Fürtig, Boris Richter, Christian Blackledge, Martin Lindorff-Larsen, Kresten Schwalbe, Harald J Am Chem Soc [Image: see text] Both experimental and theoretical structure determinations of RNAs have remained challenging due to the intrinsic dynamics of RNAs. We report here an integrated nuclear magnetic resonance/molecular dynamics (NMR/MD) structure determination approach to describe the dynamic structure of the CUUG tetraloop. We show that the tetraloop undergoes substantial dynamics, leading to averaging of the experimental data. These dynamics are particularly linked to the temperature-dependent presence of a hydrogen bond within the tetraloop. Interpreting the NMR data by a single structure represents the low-temperature structure well but fails to capture all conformational states occurring at a higher temperature. We integrate MD simulations, starting from structures of CUUG tetraloops within the Protein Data Bank, with an extensive set of NMR data, and provide a structural ensemble that describes the dynamic nature of the tetraloop and the experimental NMR data well. We thus show that one of the most stable and frequently found RNA tetraloops displays substantial dynamics, warranting such an integrated structural approach. American Chemical Society 2023-07-21 /pmc/articles/PMC10401711/ /pubmed/37479220 http://dx.doi.org/10.1021/jacs.3c03578 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Oxenfarth, Andreas Kümmerer, Felix Bottaro, Sandro Schnieders, Robbin Pinter, György Jonker, Hendrik R. A. Fürtig, Boris Richter, Christian Blackledge, Martin Lindorff-Larsen, Kresten Schwalbe, Harald Integrated NMR/Molecular Dynamics Determination of the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop |
title | Integrated NMR/Molecular
Dynamics Determination of
the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop |
title_full | Integrated NMR/Molecular
Dynamics Determination of
the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop |
title_fullStr | Integrated NMR/Molecular
Dynamics Determination of
the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop |
title_full_unstemmed | Integrated NMR/Molecular
Dynamics Determination of
the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop |
title_short | Integrated NMR/Molecular
Dynamics Determination of
the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop |
title_sort | integrated nmr/molecular
dynamics determination of
the ensemble conformation of a thermodynamically stable cuug rna tetraloop |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401711/ https://www.ncbi.nlm.nih.gov/pubmed/37479220 http://dx.doi.org/10.1021/jacs.3c03578 |
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