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

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.

Automated summary

Through atomistic molecular dynamics simulations, this study revealed the importance of molecular accumulation around DNA in influencing the stability of G-quadruplex structures. Despite TMAO partially compensating for the destabilizing effect of urea, the interaction between the two co-solutes was weak, highlighting their additive contributions. This observation provides insights for further research on selectively stabilizing DNA G-quadruplexes by modulating the concentrations of TMAO and urea in solution.