Molecular modeling of saccharides, 7. The conformation of sucrose in water: A molecular dynamics approach

Abstract

AbstractA molecular mechanics analysis of the conformational properties of sucrose in vacuo in terms of the intersaccharidic torsion angles Φ and Ψ, revealed three energy minima. The geometry of the global minimum‐energy closely resembles the solid‐state structure. Most notably, the interresidue hydrogen bonding interaction 2g‐O…︁HO‐1f present in the crystal, is retained under vacuum boundary conditions, indicating the molecular geometries adopted in the crystal lattice and in vacuo to be similar. For aqueous solutions, detailed molecular dynamics simulations of sucrose „soaked”︁ with 571 water molecules in a periodic box (truncated octahedron), revealed this direct H‐bond interaction to be replaced by an indirect, water‐mentioned one: an interresidue water‐bridge of the 2g‐O…︁H2O…︁HO‐1f type prevailed with a high significance and a long life‐time. This means the linkage geometry of sucrose in water–despite the absence of direct interresidue hydrogen bonds–again closely resembles the solid‐state and in vacuo geometry in terms of the orientation of the glucose and the fructose unit relative to one another. The solution dynamics of, and the hydration around sucrose were analyzed in terms of pair distribution functions. These indicate strong hydrogen bonding between all sucrose hydroxyls (as donors and acceptors) and water within a first, well‐defined hydration layer (hydroxyl‐oxygen–water distances 1.8–3.5 Å), whereas the acetalic oxygens are engaged to a lesser extent as H‐bond acceptors. The second hydration shell (>4 Å) is rather diffuse and less pronounced, indicating those water molecules to be in a disordered state. The implications of the hydration shell and the water bridge on the crystallization process of sucrose and on binding towards transporter proteins, and the sweet‐taste receptor, are discussed. Other sucrose conformations that may conceivably exist in aqueous solution, may have eluded the MD simulation search. The umbrella sampling technique was applied for establishing the free energy profile as a function of the intersaccharidic torsion angles. The resulting concise picture of the dynamics of sucrose in aqueous solution, encompassing the entire conformational space available, revealed only two energy minima. Of these, the by far, most populated global minimum structure corresponded to the most stable solution geometry, as found by molecular dynamics.