Understanding The Role of Reline, a Natural DES, on Temperature-Induced Conformational Changes of C-Kit G-Quadruplex DNA: A Molecular Dynamics Study.

The noncanonical guanine-rich DNAs have drawn particular attention to the scientific world due to their controllable diverse and polymorphic structures. Apart from biological and medical significance, G-quadruplex DNAs are widely used in various fields such as nanotechnology, nanomachine, biosensors, and biocatalyst. So far, the applications of the G-quadruplex DNA are mainly limited in the water medium. Recently, a new generation of solvent named deep eutectic solvent (DES) has become very popular and has been widely used as a reaction medium of biocatalytic reactions and long-term storage medium for nucleic acids, even at high temperature. Hence, it is essential to understand the role of DES on temperature-induced conformational changes of a G-quadruplex DNA. In this research work, we have explored the temperature-mediated conformational dynamics of c-kit oncogene promoter G-quadruplex DNA in reline medium in the temperature range of 300-500 K, using a total of 10 μs unbiased all-atom molecular dynamics simulation. Here, from RMSD, RMSF, Rg and principal component analyses, we notice that the c-kit G-quadruplex DNA is stable up to 450 K in reline medium. However, it unfolds in water medium at 450 K. It is found that the hydrogen bonding interactions between c-kit G-quadruplex DNA and reline play a key role in the stabilization of the G-quadruplex DNA even at high temperature. Furthermore, in this work we have observed a very interesting and distinctive phenomenon of the central cation of the G-quadruplex DNA. Its position was seen to fluctuate between the two tetrad cores, that is, the region between tetrad-1 and tetrad-2 and that between tetrad-2 and tetrad-3 and vice versa at 450 and 500 K in reline medium which is absent in water medium at 450 K. Moreover, the rate of its oscillation is increased when temperature is increased.