Differences in Conformational Sampling and Intrinsic Electric Fields Drive Ion Binding in Telomeric and TERRA G-Quadruplexes

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dc.contributor.authorPoleto, Marcelo D.en
dc.contributor.authorLemkul, Justin A.en
dc.date.accessioned2024-01-22T19:22:31Zen
dc.date.available2024-01-22T19:22:31Zen
dc.date.issued2023-10-17en
dc.description.abstractThe formation of G-quadruplexes (GQs) occurs in guanine-rich sequences of DNA and RNA, producing highly stable and structurally diverse noncanonical nucleic acid structures. GQs play crucial roles in regulating transcription, translation, and replication and maintaining the genome, among others; thus, changes to their structures can lead to diseases such as cancer. Previous studies using polarizable molecular dynamics simulations have shown differences in ion binding properties between telomeric and telomeric repeat-containing RNA GQs despite architectural similarities. Here, we used volume-based metadynamics and repulsive potential simulations in conjunction with polarizable force fields to quantify the impact of ion binding on the GQ dynamics and ion binding free energies. Furthermore, we describe how GQs exert electric fields on their surroundings to link dynamics with variations in the electronic structure. Our findings provide new insights into the energetic, physical, and conformational properties of GQs and expose subtle but important differences between DNA and RNA GQs with the same fold.en
dc.description.versionAccepted versionen
dc.format.extentPages 6851-6862en
dc.format.extent12 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier21 (Article number)en
dc.identifier.doihttps://doi.org/10.1021/acs.jcim.3c01305en
dc.identifier.eissn1549-960Xen
dc.identifier.issn1549-9596en
dc.identifier.issue21en
dc.identifier.orcidLemkul, Justin [0000-0001-6661-8653]en
dc.identifier.orcidDepolo Poleto, Marcelo [0000-0001-9210-690X]en
dc.identifier.pmid37847037en
dc.identifier.urihttps://hdl.handle.net/10919/117575en
dc.identifier.volume63en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/37847037en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.meshTelomereen
dc.subject.meshDNAen
dc.subject.meshRNAen
dc.subject.meshG-Quadruplexesen
dc.subject.meshMolecular Dynamics Simulationen
dc.titleDifferences in Conformational Sampling and Intrinsic Electric Fields Drive Ion Binding in Telomeric and TERRA G-Quadruplexesen
dc.title.serialJournal of Chemical Information and Modelingen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen

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