Modelling the DNA topology: the effect of the loop bending on G-quadruplex stability

The guanine quadruplexes are DNA/RNA guanine-rich sequences assembled into four-stranded helical structures having important roles in gene regulation and chromosome stability. Their mechanical unfolding has been generally studied with all-atom simulations, which cannot dissect the specific interactions responsible for their cohesion. Recently, we introduced a mesoscopic model able to describe the main thermal and mechanical unfolding features of the G-quadruplex, with no distinction between the different geometrical conformations forming the structure. Under the same model we study here the contribution of the bending potential in the extra-structure bonding (loops). We demonstrate with numerical simulations that the rigidity of the loops can account for the different stabilities of different topologies, specifically the parallel and the antiparallel. In the presence of the bending, the model indicates the antiparallel configuration as the most stable G4 topology, as suggested by the experiments.