Interactions of a DNA G-quadruplex with TMAO and urea: a molecular dynamics study on co-solute compensation mechanisms

Abstract

We study the individual and combined influence of TMAO and urea on a basket-type DNA G-quadruplex by means of atomistic molecular dynamics (MD) simulations. In combination with the Kirkwood–Buff theory of solutions, we propose a simple mechanism to elucidate the impact of TMAO and urea on the G-quadruplex. Our results reveal the importance of the molecular accumulation around the DNA in terms of stabilizing or destabilizing effects. The results for mixtures show only a weak interaction between both co-solutes, which highlights the additivity of contributions. Despite the fact, that TMAO can to some extent compensate the adverse impact of urea on the G-quadruplex structure, the destabilizing influence is not completely eliminated. This observation opens the door for further research on selective stabilization of DNA G-quadruplexes by modulating the concentrations of TMAO and urea in solution.