Fiasconaro, A. | Search bioRxiv

bioRxiv2018

Exact analytical solution of the extensible freely jointed chain model

Based on classical statistical mechanics, we calculate analytically the length extension under a pulling force of a polymer modeled as a freely jointed chain with extensible bonds, the latter being considered as harmonic springs. We obtain an exact formula for the extension curve, as well as an independent high force approximation. These formulas can reproduce with high precision the experimental extension/force curves also at low values of the elastic constant of the spring, where previous proposals differ substantially. We successfully validate the analytical results together with the phenomenological expressions used in the literature by analyzing the precision of their fit on data obtained from Langevin simulations.

biophysics↗

bioRxiv2017

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 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.

biophysics↗