Preferential Binding of Urea to Single-Stranded DNA Structures: A Molecular Dynamics Study.

In nature, a wide range of biological processes such as transcription termination and intermolecular binding depend on the formation of specific DNA secondary and tertiary structures. These structures can be both stabilized or destabilized by different cosolutes coexisting with nucleic acids in the cellular environment. In our molecular dynamics simulation study, we investigate the binding of urea at different concentrations to short 7-nucleotide single-stranded DNA structures in aqueous solution. The local concentration of urea around a native DNA hairpin in comparison to an unfolded DNA conformation is analyzed by a preferential binding model in light of the Kirkwood-Buff theory. All our findings indicate a pronounced accumulation of urea around DNA that is driven by a combination of electrostatic and dispersion interactions and accomplished by a significant replacement of hydrating water molecules. The outcomes of our study can be regarded as a first step into a deeper mechanistic understanding toward cosolute-induced effects on nucleotide structures in general.