Molecular dynamics studies of the hydration of alpha,alpha-trehalose

Molecular dynamics simulations have been used to model the aqueous solvation of the nonreducing sugar alpha,alpha-trehalose. The anisotropic structuring of water around the trehalose molecule was calculated in a Cartesian coordinate frame fixed with respect to the sugar molecule by averaging water positions over the trajectories and was plotted in two and three dimensions relative to the sugar. The hydrogen bonding of this sugar to solvent was calculated and compared to other sugar solutes. Hydration was required to produce the experimental conformation, through the exchange of an internal hydrogen bond for similar bonds to solvent. This equilibrium conformation was found to impose extensive structuring on the adjacent solvent, with structuring extending out to at least the third ''solvation shell'', while pure liquid water exhibits such structure only in its nearest neighbors. The details of the structuring are determined by both the specific stereochemical topology of the molecule and its conformation, with considerable interplay between conformation and solvent structure. The effect of solute flexibility on the application of this solvent density mapping technique was also examined. While the extensive solvent structural perturbation induced by the solute suggests why the sugars in general are useful antidessicants and cryoprotectants, trehalose does not appear from these results to be unique in its solvation properties. In addition, the results are consistent with the suggestion that much of the effectiveness of trehalose could result from its direct binding to biological membranes and proteins rather than from unique solution properties.