  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 forming
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.
