MOLECULAR MODELING OF SACCHARIDES .7. THE CONFORMATION OF SUCROSE IN WATER - A MOLECULAR-DYNAMICS APPROACH

A molecular mechanics analysis of the conformational properties of suc rose in vacuo in terms of the intersaccharidic torsion angles Phi and Psi revealed three energy minima. The geometry of the global minimum-e nergy closely resembles the solid-state structure. Most notably, the i nterresidue hydrogen bonding interaction 2(g)-O ... HO-1(f) 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 simu lations of sucrose ''soaked'' with 571 water molecules in a periodic b ox (truncated octahedron), revealed this direct H-bond interaction to be replaced by an indirect, water-mentioned one: an interresidue water -bridge of the 2(g)-O ... H2O ... HO-1(f) type prevailed with a high s ignificance and a long Life-time. This means the linkage geometry of s ucrose 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 relat ive 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 don ors and acceptors) and water within a first, well-defined hydration la yer (hydroxyI-oxygen - water distances 1.8-3.5 Angstrom), whereas the acetalic oxygens are engaged to a lesser extent as H-bond accepters. T he second hydration shell (>4 Angstrom) is rather diffuse and less pro nounced, indicating those water molecules to be in a disordered state. The implications of the hydration shell and the water bridge on the c rystallization process of sucrose and on binding towards transporter p roteins, and the sweet-taste receptor, are discussed. Other sucrose co nformations that may conceivably exist in aqueous solution, may have e luded the MD simulation search. The umbrella sampling technique was ap plied for establishing the free energy profile as a function of the in tersaccharidic torsion angles. The resulting concise picture of the dy namics of sucrose in aqueous solution, encompassing the entire conform ational space available, revealed only two energy minima. Of these, th e by far, most populated global minimum structure corresponded to the most stable solution geometry, as found by molecular dynamics.