Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes

[EN] Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all- atom molecular dynamics simulations with explicit solvent to analyze the mechanical unfolding of representative intramolecular G-qu...

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Detalles Bibliográficos
Autores: Bergues-Pupo, A.E., Moron, M.C., Fiasconaro, A., Falo, F., Arias-Gonzalez, J. R.|||0000-0001-6802-0874
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/152797
Acceso en línea:https://riunet.upv.es/handle/10251/152797
Access Level:acceso abierto
Palabra clave:G-quadruplex
DNA
RNA
Cation
Stability
Molecular dynamics
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Descripción
Sumario:[EN] Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all- atom molecular dynamics simulations with explicit solvent to analyze the mechanical unfolding of representative intramolecular G-quadruplex structures: a parallel, an hybrid and an antiparallel DNA and a parallel RNA, in the presence of stabilizing cations. We confirm the stability of these conformations in the presence of K+ central ions and observe distortions from the tetrad topology in their absence. Force-induced unfolding dynamics is then investigated. We show that the unfolding events in the force- extension curves are concomitant to the loss of coordination between the central ions and the guanines of the G- quadruplex. We found lower ruptures forces for the parallel configuration with respect to the antiparallel one, while the behavior of the force pattern of the parallel RNA appears similar to the parallel DNA. We anticipate that our results will be essential to interpret the fine structure rupture profiles in stretching assays at high resolution and will shed light on the mechanochemical activity of G-quadruplex-binding machinery.