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Mechanical Stability and Unfolding Pathways of Parallel Tetrameric G-Quadruplexes Probed by Pulling Simulations

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00586249" target="_blank" >RIV/68081707:_____/24:00586249 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14740/24:00138701 RIV/61989100:27740/24:10254884

  • Result on the web

    <a href="https://pubs.acs.org/doi/10.1021/acs.jcim.4c00227" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jcim.4c00227</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1021/acs.jcim.4c00227" target="_blank" >10.1021/acs.jcim.4c00227</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Mechanical Stability and Unfolding Pathways of Parallel Tetrameric G-Quadruplexes Probed by Pulling Simulations

  • Original language description

    Guanine quadruplex (GQ) is a noncanonical nucleic acid structure formed by guanine-rich DNA and RNA sequences. Folding of GQs is a complex process, where several aspects remain elusive, despite being important for understanding structure formation and biological functions of GQs. Pulling experiments are a common tool for acquiring insights into the folding landscape of GQs. Herein, we applied a computational pulling strategy-steered molecular dynamics (SMD) simulations-in combination with standard molecular dynamics (MD) simulations to explore the unfolding landscapes of tetrameric parallel GQs. We identified anisotropic properties of elastic conformational changes, unfolding transitions, and GQ mechanical stabilities. Using a special set of structural parameters, we found that the vertical component of pulling force (perpendicular to the average G-quartet plane) plays a significant role in disrupting GQ structures and weakening their mechanical stabilities. We demonstrated that the magnitude of the vertical force component depends on the pulling anchor positions and the number of G-quartets. Typical unfolding transitions for tetrameric parallel GQs involve base unzipping, opening of the G-stem, strand slippage, and rotation to cross-like structures. The unzipping was detected as the first and dominant unfolding event, and it usually started at the 3 '-end. Furthermore, results from both SMD and standard MD simulations indicate that partial spiral conformations serve as a transient ensemble during the (un)folding of GQs.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    <a href="/en/project/GA21-23718S" target="_blank" >GA21-23718S: The fascinating physical chemistry of DNA studied by advanced computations</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Chemical Information and Modeling

  • ISSN

    1549-9596

  • e-ISSN

    1549-960X

  • Volume of the periodical

    64

  • Issue of the periodical within the volume

    9

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    16

  • Pages from-to

    3896-3911

  • UT code for WoS article

    001204966100001

  • EID of the result in the Scopus database

    2-s2.0-85190742372