Rice Univesrity Logo
    • FAQ
    • Deposit your work
    • Login
    View Item 
    •   Rice Scholarship Home
    • Faculty & Staff Research
    • Faculty Publications
    • View Item
    •   Rice Scholarship Home
    • Faculty & Staff Research
    • Faculty Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Simulation-guided DNA probe design for consistently ultraspecific hybridization

    Thumbnail
    Name:
    DNA-Probe-Design.pdf
    Size:
    4.650Mb
    Format:
    PDF
    View/Open
    Author
    Wang, Juexiao Sherry; Zhang, David Yu
    Date
    2015
    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.
    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.
    Published Version
    http://dx.doi.org/10.1038/nchem.2266
    Type
    Journal article
    Publisher
    Springer Nature
    Citable link to this page
    https://hdl.handle.net/1911/94226
    Rights
    This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer Nature.
    Metadata
    Show full item record
    Collections
    • Bioengineering Publications [632]
    • Faculty Publications [4988]

    Home | FAQ | Contact Us | Privacy Notice | Accessibility Statement
    Managed by the Digital Scholarship Services at Fondren Library, Rice University
    Physical Address: 6100 Main Street, Houston, Texas 77005
    Mailing Address: MS-44, P.O.BOX 1892, Houston, Texas 77251-1892
    Site Map

     

    Searching scope

    Browse

    Entire ArchiveCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsTypeThis CollectionBy Issue DateAuthorsTitlesSubjectsType

    My Account

    Login

    Statistics

    View Usage Statistics

    Home | FAQ | Contact Us | Privacy Notice | Accessibility Statement
    Managed by the Digital Scholarship Services at Fondren Library, Rice University
    Physical Address: 6100 Main Street, Houston, Texas 77005
    Mailing Address: MS-44, P.O.BOX 1892, Houston, Texas 77251-1892
    Site Map