Essential Dynamics of Ubiquitin in Water and in a Natural Deep Eutectic Solvent

Natural deep eutectic solvents (NADESs) comprised of osmolytes are of interest as potential biomolecular (cryo)protectants. However, the way these solvents influence the structure and dynamics of biomolecules as well as the role of water remains poorly understood. We carried out principal component analysis of various secondary structure elements of ubiquitin in water and a betaine:glycerol:water (1:2:;z = 0, 1, 2, 5, 10, 20, 45) NADES, from molecular dynamics trajectories, to gain insight into the protein dynamics as it undergoes a transition from a highly viscous anhydrous to an aqueous environment. A crossover of the protein’s essential dynamics at z ~ 5, induced by solvent-shell coupled fluctuations, is observed, indicating that ubiquitin should (re)fold in the NADES upon water addition at z > ~ 5. Further, in contrast to water, the anhydrous NADES preserves ubiquitin’s essential modes at high temperatures explaining the protein’s enhanced thermal stability.