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2017 ; 7
(1
): 11756
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Mesoscopic model for DNA G-quadruplex unfolding
#MMPMID28924219
Bergues-Pupo AE
; Gutiérrez I
; Arias-Gonzalez JR
; Falo F
; Fiasconaro A
Sci Rep
2017[Sep]; 7
(1
): 11756
PMID28924219
show ga
Genomes contain rare guanine-rich sequences capable of assembling into
four-stranded helical structures, termed G-quadruplexes, with potential roles in
gene regulation and chromosome stability. Their mechanical unfolding has only
been reported to date by all-atom simulations, which cannot dissect the major
physical interactions responsible for their cohesion. Here, we propose a
mesoscopic model to describe both the mechanical and thermal stability of DNA
G-quadruplexes, where each nucleotide of the structure, as well as each central
cation located at the inner channel, is mapped onto a single bead. In this
framework we are able to simulate loading rates similar to the experimental ones,
which are not reachable in simulations with atomistic resolution. In this regard,
we present single-molecule force-induced unfolding experiments by a
high-resolution optical tweezers on a DNA telomeric sequence capable of adopting
a G-quadruplex conformation. Fitting the parameters of the model to the
experiments we find a correct prediction of the rupture-force kinetics and a good
agreement with previous near equilibrium measurements. Since G-quadruplex
unfolding dynamics is halfway in complexity between secondary nucleic acids and
tertiary protein structures, our model entails a nanoscale paradigm for
non-equilibrium processes in the cell.
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