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Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study

Riboswitches are mRNA-based molecules capable of controlling the expression of genes. They undergo conformational changes upon ligand binding, and as a result, they inhibit or promote the expression of the associated gene. The close connection between structural rearrangement and function makes a de...

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Detalles Bibliográficos
Autores principales: Allnér, Olof, Nilsson, Lennart, Villa, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683926/
https://www.ncbi.nlm.nih.gov/pubmed/23716711
http://dx.doi.org/10.1261/rna.037549.112
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author Allnér, Olof
Nilsson, Lennart
Villa, Alessandra
author_facet Allnér, Olof
Nilsson, Lennart
Villa, Alessandra
author_sort Allnér, Olof
collection PubMed
description Riboswitches are mRNA-based molecules capable of controlling the expression of genes. They undergo conformational changes upon ligand binding, and as a result, they inhibit or promote the expression of the associated gene. The close connection between structural rearrangement and function makes a detailed knowledge of the molecular interactions an important step to understand the riboswitch mechanism and efficiency. We have performed all-atom molecular dynamics simulations of the adenine-sensing add A-riboswitch to study the breaking of the kissing loop, one key tertiary element in the aptamer structure. We investigated the aptamer domain of the add A-riboswitch in complex with its cognate ligand and in the absence of the ligand. The opening of the hairpins was simulated using umbrella sampling using the distance between two loops as the reaction coordinate. A two-step process was observed in all the simulated systems. First, a general loss of stacking and hydrogen bond interactions is seen. The last interactions that break are the two base pairs G37-C61 and G38-C60, but the break does not affect the energy profile, indicating their pivotal role in the tertiary structure formation but not in the structure stabilization. The junction area is partially organized before the kissing loop formation and residue A24 anchors together the loop helices. Moreover, when the distance between the loops is increased, one of the hairpins showed more flexibility by changing its orientation in the structure, while the other conserved its coaxial arrangement with the rest of the structure.
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spelling pubmed-36839262013-07-01 Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study Allnér, Olof Nilsson, Lennart Villa, Alessandra RNA Articles Riboswitches are mRNA-based molecules capable of controlling the expression of genes. They undergo conformational changes upon ligand binding, and as a result, they inhibit or promote the expression of the associated gene. The close connection between structural rearrangement and function makes a detailed knowledge of the molecular interactions an important step to understand the riboswitch mechanism and efficiency. We have performed all-atom molecular dynamics simulations of the adenine-sensing add A-riboswitch to study the breaking of the kissing loop, one key tertiary element in the aptamer structure. We investigated the aptamer domain of the add A-riboswitch in complex with its cognate ligand and in the absence of the ligand. The opening of the hairpins was simulated using umbrella sampling using the distance between two loops as the reaction coordinate. A two-step process was observed in all the simulated systems. First, a general loss of stacking and hydrogen bond interactions is seen. The last interactions that break are the two base pairs G37-C61 and G38-C60, but the break does not affect the energy profile, indicating their pivotal role in the tertiary structure formation but not in the structure stabilization. The junction area is partially organized before the kissing loop formation and residue A24 anchors together the loop helices. Moreover, when the distance between the loops is increased, one of the hairpins showed more flexibility by changing its orientation in the structure, while the other conserved its coaxial arrangement with the rest of the structure. Cold Spring Harbor Laboratory Press 2013-07 /pmc/articles/PMC3683926/ /pubmed/23716711 http://dx.doi.org/10.1261/rna.037549.112 Text en © 2013; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/3.0/ This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/. Freely available online through the RNA Open Access option.
spellingShingle Articles
Allnér, Olof
Nilsson, Lennart
Villa, Alessandra
Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study
title Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study
title_full Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study
title_fullStr Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study
title_full_unstemmed Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study
title_short Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study
title_sort loop–loop interaction in an adenine-sensing riboswitch: a molecular dynamics study
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683926/
https://www.ncbi.nlm.nih.gov/pubmed/23716711
http://dx.doi.org/10.1261/rna.037549.112
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