Urea-aromatic interactions in biology

Noncovalent interactions are key determinants in both chemical and biological processes. Among such processes, the hydrophobic interactions play an eminent role in folding of proteins, nucleic acids, formation of membranes, protein-ligand recognition, etc.. Though this interaction is mediated through the aqueous solvent, the stability of the above biomolecules can be highly sensitive to any small external perturbations, such as temperature, pressure, pH, or even cosolvent additives, like, urea-a highly soluble small organic molecule utilized by various living organisms to regulate osmotic pressure. A plethora of detailed studies exist covering both experimental and theoretical regimes, to understand how urea modulates the stability of biological macromolecules. While experimentalists have been primarily focusing on the thermodynamic and kinetic aspects, theoretical modeling predominantly involves mechanistic information at the molecular level, calculating atomistic details applying the force field approach to the high level electronic details using the quantum mechanical methods. The review focuses mainly on examples with biological relevance, such as (1) urea-assisted protein unfolding, (2) urea-assisted RNA unfolding, (3) urea lesion interaction within damaged DNA, (4) urea conduction through membrane proteins, and (5) protein-ligand interactions those explicitly address the vitality of hydrophobic interactions involving exclusively the urea-aromatic moiety.