How Does Aqueous Choline‑<i>O</i>‑Sulfate Solution Nullify the Action of Urea in Protein Denaturation?

Choline-O-sulfate (COS) acts as a protecting osmolyte in several plants, fungal, and bacterial species. Classical molecular dynamics simulation is performed to examine the molecular mechanism by which COS molecules counteract urea-conferred denaturation of the S-peptide analogue. The calculations of root mean square deviation, the radius of gyration of the Cα atom, and the solvent accessible surface area of the peptide heavy atoms imply that the 4–12 residues of the peptide in pure water remain in helical conformation at 310 K temperature. But, in binary ∼8 M aqueous urea solution the peptide loses its native conformation. Interestingly, in the ternary peptide–urea–COS system with 0.30 M COS concentration, the native conformation of the peptide remains preserved. The estimation of the average number of hydrogen bonds between different solution species indicates that it is the preferential urea–COS interactions, which influence peptide–urea interactions significantly. This observation is further confirmed by the calculation of atomic density map of urea around the peptide heavy atoms and time-averaged relative local distribution functions involving peptide and urea. Moreover, the exclusion of COS molecules from the peptide surface is also confirmed by the determination of the number of COS molecules in the first solvation shell of the peptide as well as from the calculated time-averaged relative local distribution functions involving peptide and COS. A sharp drop in the diffusion coefficient values of all solution species is observed as COS is added. These findings suggest that it is the preferential solvation of urea molecule by COS, which makes the former (urea) less available for the peptide to show its deleterious effect and hence the native conformation of the peptide is retained