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dc.contributor.authorWang, Juexiao Sherry
Zhang, David Yu
dc.date.accessioned 2017-05-12T15:04:32Z
dc.date.available 2017-05-12T15:04:32Z
dc.date.issued 2015
dc.identifier.citation Wang, Juexiao Sherry and Zhang, David Yu. "Simulation-guided DNA probe design for consistently ultraspecific hybridization." Nature Chemistry, 7, (2015) Springer Nature: 545-553. http://dx.doi.org/10.1038/nchem.2266.
dc.identifier.urihttps://hdl.handle.net/1911/94226
dc.description.abstract Hybridization 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.
dc.language.iso eng
dc.publisher Springer Nature
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer Nature.
dc.title Simulation-guided DNA probe design for consistently ultraspecific hybridization
dc.type Journal article
dc.citation.journalTitle Nature Chemistry
dc.contributor.org Systems, Synthetic, and Physical Biology
dc.citation.volumeNumber 7
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1038/nchem.2266
dc.identifier.pmcid PMC4479422
dc.identifier.pmid 26100802
dc.type.publication post-print
dc.citation.firstpage 545
dc.citation.lastpage 553


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