Simulation-guided DNA probe design for consistently ultraspecific hybridization

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dc.citation.firstpage545en_US
dc.citation.journalTitleNature Chemistryen_US
dc.citation.lastpage553en_US
dc.citation.volumeNumber7en_US
dc.contributor.authorWang, Juexiao Sherryen_US
dc.contributor.authorZhang, David Yuen_US
dc.contributor.orgSystems, Synthetic, and Physical Biologyen_US
dc.date.accessioned2017-05-12T15:04:32Zen_US
dc.date.available2017-05-12T15:04:32Zen_US
dc.date.issued2015en_US
dc.description.abstractHybridization of complementary sequences is one of the central tenets of nucleic acid chemistry; however, the unintended binding of closely related sequences limits the accuracy of hybridization-based approaches to analysing nucleic acids. Thermodynamics-guided probe design and empirical optimization of the reaction conditions have been used to enable the discrimination of single-nucleotide variants, but typically these approaches provide only an approximately 25-fold difference in binding affinity. Here we show that simulations of the binding kinetics are both necessary and sufficient to design nucleic acid probe systems with consistently high specificity as they enable the discovery of an optimal combination of thermodynamic parameters. Simulation-guided probe systems designed against 44 sequences of different target single-nucleotide variants showed between a 200- and 3,000-fold (median 890) higher binding affinity than their corresponding wild-type sequences. As a demonstration of the usefulness of this simulation-guided design approach, we developed probes that, in combination with PCR amplification, detect low concentrations of variant alleles (1%) in human genomic DNA.en_US
dc.identifier.citationWang, Juexiao Sherry and Zhang, David Yu. "Simulation-guided DNA probe design for consistently ultraspecific hybridization." <i>Nature Chemistry,</i> 7, (2015) Springer Nature: 545-553. http://dx.doi.org/10.1038/nchem.2266.en_US
dc.identifier.doihttp://dx.doi.org/10.1038/nchem.2266en_US
dc.identifier.urihttps://hdl.handle.net/1911/94226en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer Nature.en_US
dc.titleSimulation-guided DNA probe design for consistently ultraspecific hybridizationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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