Trehalose induced modifications in the solvation pattern of N-methylacetamide

We have carried out molecular dynamics simulation to investigate the role of trehalose molecules on the change in the structural and dynamical properties of aqueous N-methylacetamide (NMA) solution. In this study, we considered six different trehalose concentrations ranging from 0 to 66%. Results are discussed in the framework of hydrophobic interactions between different methyl groups of NMA, structure of the solutions, and hydrogen bonding interactions between different solution species. We observe that the propensity of hydrophobic association through the methyl groups of NMA is essentially insensitive to trehalose concentration except for higher trehalose concentration where the hydrophobic interactions between the hydrophobic methyl groups are getting reduced. Also observed are (i) trehalose induced slight collapse of the second hydration shell of water, (ii) presence of excess water molecules near NMA, and (iii) exclusion of trehalose from NMA. Our NMA-water radial distribution function analyses followed by average number of hydrogen bonds per NMA calculations reveal that, in the hydration of NMA molecules, its carbonyl group oxygen (over amide hydrogen) is predominantly involved. As trehalose is added, we observe, in accordance with the water replacement hypothesis, the replacement of water-NMA hydrogen bonds by NMA-trehalose hydrogen bonds, keeping the average number of hydrogen bonds formed by a single NMA with different solution species essentially unchanged. Our hydrogen bond calculations further reveal that addition of trehalose replaces water-NMA hydrogen bonds by water-trehalose hydrogen bonds. And as a result, we find that the average number of hydrogen bonds formed by a water molecule remain unchanged. We also find that addition of trehalose decreases the translational motion of all the solution species sharply.