Microscopic Understanding of DNA Groove Binding by Hydrophilic and Hydrophobic Ionic Liquids

In addition to being biologically essential macromolecules, DNAs in duplex forms also have extensive biotechnological applications. DNA preservation is critical for any biotechnological use; however, long-term stability under ambient conditions remains challenging. Aqueous ionic liquid (IL) solutions have evolved as excellent storage media for nucleic acid samples in recent times. In this work, we have systematically investigated the interaction patterns of a series of glycinate-based ILs containing cations with varying hydrophilic and hydrophobic characteristics with duplex B-DNA using atomistic molecular dynamics (MD) simulations. The calculations revealed subtle local conformational modifications of the DNA in the presence of the ILs, though the overall DNA structure remained largely conserved. Besides, it is demonstrated that the presence of the ILs leads to nonuniform expulsion of water molecules from the minor and the major grooves of the DNA. Specifically, the propensity to exchange water molecules by the IL components is higher from the more constricted minor groove than that from the wider major groove. Furthermore, due to geometrical constraints and consequent stronger negative potential, a high degree of specificity in cation orientations and bindings has been observed within the minor groove as compared to random nonspecific cation orientations in the major groove. Importantly, an increased fraction of DNA-water hydrogen bond breaking within the minor groove in the presence of the IL cations, as compared to that in the major groove, is the microscopic origin behind such nonuniform effects on solvent properties in the two grooves.