Effects of ethanol on the secondary structure specific hydration properties of Chymotrypsin Inhibitor 2 in its folded and unfolded forms

Molecular dynamics simulations were performed for the protein Chymotrypsin Inhibitor 2 in water–ethanol binary mixtures at several ethanol concentrations at two different temperatures to explore the differential role of ethanol on the hydration properties of the secondary structural segments of the protein. We find that, compared to the water structure around the secondary structure segments of the unfolded protein in pure water, water molecules preferred to be structured more in presence of ethanol. The structuration of ethanol is noticed to be higher around helix and sheet, as compared to that around the loop. The differential slow structural relaxations of the hydrogen bonds involving the secondary structural segments of protein in water–ethanol mixed solutions, as compared to that in pure water infer that ethanol alters the water properties in a remarkable manner. The slow relaxations of the hydrogen bonds formed between ethanol and the secondary structural segments of the protein, in general, suggests that ethanol interacts directly with the protein. However, the relatively faster relaxation of the ethanol-segment hydrogen bonds involving unfolded protein as compared to that involving the folded protein suggests that the unfolded protein surface can remain dynamically free to interact with water more.