Mesoscopic model for DNA G-quadruplex unfolding.

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.

Thermal and inertial resonances in DNA unzipping.

Single-molecule experiments combined with alternate forces are able to provide useful information not present in standard constant-force and -velocity pulling protocols. Here, we study the effects of such forces in the DNA mechanical unzipping by using an extension of the Peyrard-Bishop-Dauxois model. By changing the damping regime in the dynamical equations, we obtained two resonant mechanisms in both the mean time and the mean force of unzipping. One is thermally assisted and it is characterized by a matching between the period of the external force and the mean unzipping time of the DNA chain, while the other depends on the inertial properties of the system. Both mechanisms are studied systematically under different opening protocols and different parameters of the system. The main results here presented contribute in characterizing and finding optimized conditions in DNA unzipping experiments.

Modeling the interaction of DNA with alternating fields.

We study the influence of a terahertz field on thermal properties of DNA molecules. A Peyrard-Bishop-Dauxois model with the inclusion of a solvent interaction term is considered. The terahertz field is included as a sinusoidal driven force in the equation of motion. We show how under certain field and system parameters, the melting transition and bubble formation are modified.