Ion-Dependent Conformational Plasticity of Telomeric G-Hairpins and G-Quadruplexes

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dc.contributor.authorSalsbury, Alexa M.en
dc.contributor.authorMichel, Haley M.en
dc.contributor.authorLemkul, Justin A.en
dc.date.accessioned2022-11-10T15:06:00Zen
dc.date.available2022-11-10T15:06:00Zen
dc.date.issued2022-07-12en
dc.description.abstractTelomeric DNA is guanine-rich and can adopt structures such as G-quadruplexes (GQs) and G-hairpins. Telomeric GQs influence genome stability and telomerase activity, making understanding of enzyme-GQ interactions and dynamics important for potential drug design. GQs have a characteristic tetrad core, which is connected by loop regions. Within this architecture are G-hairpins, fold back motifs that are thought to represent the first intermediate in GQ folding. To better understand the relationship between G-hairpin motifs and GQs, we performed polarizable simulations of a two-tetrad telomeric GQ and an isolated SC11 telomeric G-hairpin. The telomeric GQ contains a G-triad, which functions as part of the tetrad core or linker regions, depending on local conformational change. This triad and another motif below the tetrad core frequently bound ions and may represent druggable sites. Further, we observed the unbiased formation of a G-triad and a G-tetrad in simulations of the SC11 G-hairpin and found that cations can be partially hydrated while facilitating the formation of these motifs. Finally, we demonstrated that K+ ions form specific interactions with guanine bases, while Na+ ions interact nonspecifically with bases in the structure. Together, these simulations provide new insights into the influence of ions on GQs, G-hairpins, and G-triad motifs.en
dc.description.notesThis work was supported by the National Institutes of Health (grant R35GM133754 to J.A.L.) , the Thomas F. and Kate Miller Jeffress Memorial Trust (Bank of America, Trustee) , USDA-NIFA (project number VA-160092 to J.A.L.) , and The American Association of University Women (American Dissertation Fellowship to A.M.S.) .en
dc.description.sponsorshipNational Institutes of Health [R35GM133754]; USDA-NIFA [VA-160092]; American Association of University Women (American Dissertation Fellowship); Thomas F. and Kate Miller Jeffress Memorial Trust (Bank of America)en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1021/acsomega.2c01600en
dc.identifier.issn2470-1343en
dc.identifier.issue27en
dc.identifier.pmid35847338en
dc.identifier.urihttp://hdl.handle.net/10919/112555en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectmolecular-dynamics simulationsen
dc.subjectpolarizable force-fielden
dc.subjectnucleic-acidsen
dc.subjectk+ solutionen
dc.subjectthermodynamic analysisen
dc.subjectfolding pathwaysen
dc.subjectg-triplexen
dc.subjectdnaen
dc.subjectguanineen
dc.subjectwateren
dc.titleIon-Dependent Conformational Plasticity of Telomeric G-Hairpins and G-Quadruplexesen
dc.title.serialACS Omegaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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