Protein Stability in a Natural Deep Eutectic Solvent: Preferential Hydration or Solvent Slaving?

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Abstract
Deep eutectic solvents (DESs) emerged as potential alternative solvent media in multiple areas, including biomolecular (cryo)preservation. Herein, we studied the stability of a small protein (ubiquitin) in water and a betaine-glycerol-water (B:G:W) (1:2:z; z = 0, 1, 2, 5, 10) DES, through molecular dynamics. An AMBER-based model that accurately describes the density and shear viscosity of the DES is proposed. We find that water molecules are largely trapped in the solvent, precluding the formation of a full hydration layer, seemingly opposite to osmolytes’ preferential exclusion/preferential hydration mechanism. Whereas the protein is stable in the DES, structural fluctuations are largely suppressed and only recovered upon sufficient hydration. This is explained by a solvent-slaving mechanism where -fluctuations are key, also explaining the non-monotonic folding of some proteins in aqueous DESs. A thermal stability enhancement in the DES is also observed, caused by a similar slowdown of the backbone torsional dynamics. Our results support a kinetic stabilization of the protein in the DES, whereas a possible thermodynamic stabilization does not follow a preferential hydration or water entrapment mechanism.
Funding Information
  • Fundação para a Ciência e a Tecnologia (CEECIND/00821/2017)
  • Fundação para a Ciência e a Tecnologia (UIDB/04046/2020)
  • Fundação para a Ciência e a Tecnologia (UIDP/04046/2020)

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