Effect of Hydrated and Nonhydrated Choline Chloride–Urea Deep Eutectic Solvent (Reline) on Thrombin-Binding G-quadruplex Aptamer (TBA): A Classical Molecular Dynamics Simulation Study

Guanine-rich quadruplex nucleic acid (G-DNA) sequence is highly polymorphic. The obtained structure of G-DNA is exquisitely impressible to its sequence and the chemical environment. Due to its controllable different structures, G-DNA has acquired much attention in various research areas such as nanotechnology, medicinal chemistry, and molecular biology. However, the applications of G-DNA are mainly restricted to the aqueous media, although a large number of important chemical reactions, nanodevices, etc. have also been carried out in purely water-free medium. Recently, deep eutectic solvents (DESs) such as choline–urea (1:2) eutectic mixture, namely, reline, has widely been used as a reaction medium and also water-free storage medium for biological systems like different types of nucleic acids. Hence, it is very important to figure out the effect of the deep eutectic solvent with DNA. In this research work, we have discussed the interaction between reline with guanine-rich quadruplex thrombin-binding aptamer (TBA) DNA at 300 K, for different reline concentrations. To understand the conformational behavior of quadruplex TBA in reline DES, we have performed 10 μs all-atom molecular dynamics simulations. Here, we note that the structure of TBA deviates much more from its NMR structure at low reline concentrations. In other way, at high reline concentrations, the quadruplex TBA is much more rigid or less flexible than comparatively lower reline concentrations. Moreover, from the spatial distribution function study, the density of reline is higher near sugar phosphate backbone region than the others. Furthermore, at lower reline concentrations, guanine-8 and thymine-9 of loop-2 stack to each other, which is not noted at higher reline concentrations.