MOLECULAR-DYNAMICS STUDIES OF THE HYDRATION OF ALPHA,ALPHA-TREHALOSE

Molecular dynamics simulations have been used to model the aqueous sol vation 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 o f this sugar to solvent was calculated and compared to other sugar sol utes. Hydration was required to produce the experimental conformation, through the exchange of an internal hydrogen bond for similar bonds t o solvent. This equilibrium conformation was found to impose extensive structuring on the adjacent solvent, with structuring extending out t o at least the third ''solvation shell'', while pure liquid water exhi bits such structure only in its nearest neighbors. The details of the structuring are determined by both the specific stereochemical topolog y of the molecule and its conformation, with considerable interplay be tween conformation and solvent structure. The effect of solute flexibi lity on the application of this solvent density mapping technique was also examined. While the extensive solvent structural perturbation ind uced by the solute suggests why the sugars in general are useful antid essicants and cryoprotectants, trehalose does not appear from these re sults to be unique in its solvation properties. In addition, the resul ts are consistent with the suggestion that much of the effectiveness o f trehalose could result from its direct binding to biological membran es and proteins rather than from unique solution properties.