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Exploring the Dynamics of Propeller Loops in Human Telomeric DNA Quadruplexes Using Atomistic Simulations

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00485734" target="_blank" >RIV/68081707:_____/17:00485734 - isvavai.cz</a>

  • Alternative codes found

    RIV/61989592:15310/17:73584502

  • Result on the web

    <a href="http://dx.doi.org/10.1021/acs.jctc.7b00226" target="_blank" >http://dx.doi.org/10.1021/acs.jctc.7b00226</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1021/acs.jctc.7b00226" target="_blank" >10.1021/acs.jctc.7b00226</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Exploring the Dynamics of Propeller Loops in Human Telomeric DNA Quadruplexes Using Atomistic Simulations

  • Original language description

    We have carried out a series of extended unbiased molecular dynamics (MD) simulations (up to 10 its long, similar to 162 mu s in total) complemented by replica-exchange with the collective variable tempering (RECT) approach for several human telomeric DNA G-quadruplex (GQ) topologies with TTA propeller loops. We used different AMBER DNA force-field variants and also processed simulations by Markov State Model (MSM) analysis. The slow conformational transitions in the propeller loops took place on a scale of a few,us, emphasizing the need for long simulations in studies of GQ dynamics. The propeller loops sampled similar ensembles for all GQtopologies and for all force field dihedral-potential variants. The outcomes of standard and RECT simulations were consistent and captured similar spectrum of loop conformations. However, the most common crystallographic loop conformation was very unstable with all force-field versions. Although the loss of canonical gamma-trans state of the first propeller loop nucleotide could be related to the indispensable bsc0 alpha/gamma dihedral potential, even supporting this particular dihedral by a bias was insufficient to populate the experimentally dominant loop conformation. In conclusion, while our simulations were capable of providing a reasonable albeit not converged sampling of the TTA propeller loop conformational space, the force-field description still remained far from satisfactory.

  • 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

    10403 - Physical chemistry

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2017

  • 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 Theory and Computation

  • ISSN

    1549-9618

  • e-ISSN

  • Volume of the periodical

    13

  • Issue of the periodical within the volume

    6

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    23

  • Pages from-to

    2458-2480

  • UT code for WoS article

    000403530100010

  • EID of the result in the Scopus database