Molecular dynamics simulations reveal the parallel stranded d (GGGA)3GGG DNA quadruplex folds via multiple paths from a coil-like ensemble
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00584664" target="_blank" >RIV/68081707:_____/24:00584664 - isvavai.cz</a>
Alternative codes found
RIV/61989100:27740/24:10254885
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0141813024005154?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0141813024005154?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ijbiomac.2024.129712" target="_blank" >10.1016/j.ijbiomac.2024.129712</a>
Alternative languages
Result language
angličtina
Original language name
Molecular dynamics simulations reveal the parallel stranded d (GGGA)3GGG DNA quadruplex folds via multiple paths from a coil-like ensemble
Original language description
G-quadruplexes (G4s) are non-canonical nucleic acid structures that fold through complex processes. Characterization of the G4 folding landscape may help to elucidate biological roles of G4s but is challenging both experimentally and computationally. Here, we achieved complete folding of a three-quartet parallel DNA G4 with (GGGA)3GGG sequence using all-atom explicit-solvent enhanced-sampling molecular dynamics (MD) simulations. The simulations suggested early formation of guanine stacks in the G-tracts, which behave as semi-rigid blocks in the folding process. The folding continues via the formation of a collapsed compact coil-like ensemble. Structuring of the G4 from the coil then proceeds via various cross-like, hairpin, slip-stranded and two-quartet ensembles and can bypass the G-triplex structure. Folding of the parallel G4 does not appear to involve any salient intermediates and is a multi-pathway process. We also carried out an extended set of simulations of parallel G-hairpins. While parallel G-hairpins are extremely unstable when isolated, they are more stable inside the coil structure. On the methodology side, we show that the AMBER DNA force field predicts the folded G4 to be less stable than the unfolded ensemble, uncovering substantial force-field issues. Overall, we provide unique atomistic insights into the folding landscape of parallel-stranded G4 but also reveal limitations of current state-ofthe-art MD techniques.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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
International Journal of Biological Macromolecules
ISSN
0141-8130
e-ISSN
1879-0003
Volume of the periodical
261
Issue of the periodical within the volume
2024-03-22
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
15
Pages from-to
129712
UT code for WoS article
001176500400001
EID of the result in the Scopus database
2-s2.0-85183987821