Influence of temperature on the solvation of N-methylacetamide in aqueous trehalose solution: A molecular dynamics simulation study

Abstract

We report molecular dynamics simulation results of aqueous solution of NMA both in the presence and absence of trehalose at five different temperatures ranging from 285K to 345K at 1atm pressure. For each temperature, we consider six different trehalose concentrations ranging from 0% to 66%. For a given temperature, we find the accumulation of more than expected water molecules in the first solvation shell of hydrophobic methyl group of NMA when trehalose concentration is very high. Further, our calculations of hydrogen bond properties reveal the formation of more and more trehalose–NMA hydrogen bonds and the breaking of water–NMA hydrogen bonds as trehalose concentration is increased. Interestingly, the breaking of NMA–water hydrogen bonds is well compensated by the formation of NMA–trehalose hydrogen bonds keeping the total number of hydrogen bonds formed by a single NMA molecule to remain unchanged. These observations are in accordance with water replacement hypothesis. Though we observe that temperature induced breaking of water–trehalose hydrogen bonds, remarkably, water–water and trehalose–trehalose hydrogen bonds tend to offset the effect of temperature when trehalose concentration is high. This implies that in a concentrated solution at higher temperature trehalose molecules play a minor role by reducing the number of water molecules available for protein. The calculated site–site distribution functions involving NMA and water molecules show that the former prefers to act as acceptor and not as a donor when it forms hydrogen bonds with water. Further, in consistent with the previously reported results (N. T. Skipper, Chem. Phys. Lett, 207 (1993) 424), we find that temperature induced slight breaking of water structure whereas, a prominent enhancement in the water structure is observed as trehalose concentration increases. The translational motion of different solution species increases with increasing temperature. On the other hand, trehalose induced retardation in the diffusion coefficient values for different solution species with more profound effect for trehalose and NMA molecules are observed. Also observed are: (a) enhancement in the trehalose–trehalose hydrogen bond network as trehalose concentration increases and (b) the presence of NMA molecules in the cluster of trehalose.