• Login
    View Item 
    •   Home
    • Research
    • Articles
    • View Item
    •   Home
    • Research
    • Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of KAUSTCommunitiesIssue DateSubmit DateThis CollectionIssue DateSubmit Date

    My Account

    Login

    Quick Links

    Open Access PolicyORCID LibguideTheses and Dissertations LibguideSubmit an Item

    Statistics

    Display statistics

    Replacing Thymine with a Strongly Pairing Fifth Base: a Combined Quantum Mechanics and Molecular Dynamics Study

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Replacing thymine-1-s2.0-S200103702100057X-main.pdf
    Size:
    3.021Mb
    Format:
    PDF
    Description:
    Accepted Article
    Download
    Type
    Article
    Authors
    Chawla, Mohit cc
    Gorle, Suresh cc
    Shaikh, Abdul Rajjak
    Oliva, Romina
    Cavallo, Luigi cc
    KAUST Department
    Biological and Environmental Science and Engineering (BESE) Division
    Chemical Science Program
    KAUST Catalysis Center (KCC)
    Physical Science and Engineering (PSE) Division
    Date
    2021-02-23
    Online Publication Date
    2021-02-23
    Print Publication Date
    2021
    Embargo End Date
    2022-02-23
    Submitted Date
    2020-12-04
    Permanent link to this record
    http://hdl.handle.net/10754/667656
    
    Metadata
    Show full item record
    Abstract
    The non-natural ethynylmethylpyridone C-nucleoside (W), a thymidine (T) analogue that can be incorporated in oligonucleotides by automated synthesis, has recently been reported to form a high fidelity base pair with adenosine (A) and to be well accommodated in B-DNA duplexes. The enhanced binding affinity for A of W, as compared to T, makes it an ideal modification for biotechnological applications, such as efficient probe hybridization for the parallel detection of multiple DNA strands. In order to complement the experimental study and rationalize the impact of the non-natural W nucleoside on the structure, stability and dynamics of DNA structures, we performed quantum mechanics (QM) calculations along with molecular dynamics (MD) simulations. Consistently with the experimental study, our QM calculations show that the A:W base pair has an increased stability as compared to the natural A:T pair, due to an additional CH-π interaction. Furthermore, we show that mispairing between W and guanine (G) causes a distortion in the planarity of the base pair, thus explaining the destabilization of DNA duplexes featuring a G:W pair. MD simulations show that incorporation of single or multiple consecutive A:W pairs in DNA duplexes causes minor changes to the intra- and inter-base geometrical parameters, while a moderate widening/shrinking of the major/minor groove of the duplexes is observed. QM calculations applied to selected stacks from the MD simulations also show an increased stacking energy for W, over T, with the neighboring bases.
    Citation
    Chawla, M., Gorle, S., Rajjak Shaikh, A., Oliva, R., & Cavallo, L. (2021). Replacing Thymine with a Strongly Pairing Fifth Base: a Combined Quantum Mechanics and Molecular Dynamics Study. Computational and Structural Biotechnology Journal. doi:10.1016/j.csbj.2021.02.006
    Sponsors
    L.C. and M. C. acknowledges King Abdullah University of Science and Technology (KAUST) for support and the KAUST Supercomputing Laboratory for providing computational resources of the supercomputer Shaheen II. R.O. thanks MIUR-FFABR (Fondo per il Finanziamento Attività Base di Ricerca) for funding.
    Publisher
    Elsevier BV
    Journal
    Computational and Structural Biotechnology Journal
    DOI
    10.1016/j.csbj.2021.02.006
    Additional Links
    https://linkinghub.elsevier.com/retrieve/pii/S200103702100057X
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.csbj.2021.02.006
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Physical Science and Engineering (PSE) Division; Chemical Science Program; KAUST Catalysis Center (KCC)

    entitlement

     
    DSpace software copyright © 2002-2022  DuraSpace
    Quick Guide | Contact Us | KAUST University Library
    Open Repository is a service hosted by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items. For anonymous users the allowed maximum amount is 50 search results.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.