Solvent interactions determine carbohydrate conformation

The relationship between the three-dimensional structures of oligosaccharid es and polysaccharides and their biological properties has been the focus o f many recent studies. The overall conformation of an oligosaccharide depen ds primarily on the orientation of the torsion angles (phi, psi, and omega) between glycosyl residues. Numerous experimental studies have shown that i n glucopyranosides the omega -torsion angle (O-6-C-6-C-5-O-5) displays a pr eference for gauche orientations, in disagreement with predictions based on gas-phase quantum mechanics calculations. In contrast, the omega -angle in galactopyranosides displays a high proportion of the anti-orientation. For oligosaccharides containing glycosidic linkages at the 6-position (1 -->6 linked), variations in rotamer population have a direct effect on the oligo saccharides' structure and function, and yet the physical origin of these c onformational preferences remains unclear. Although it is generally recogni zed that the gauche effect in carbohydrates is a solvent-dependent phenomen on, the mechanism through which solvent induces the gauche preference is no t understood. In the present work, quantum mechanics and solvated molecular dynamics calculations were performed on two representative carbohydrates, methyl alpha -D-glucopyranoside and methyl alpha -D-galactopyranoside. We s how that correct reproduction of the experimental rotamer distributions abo ut the omega -angles is obtained only after explicit water is included in t he molecular dynamics simulations. The primary role of the water appears to be to disrupt the hydrogen bonding within the carbohydrate, thereby allowi ng the rotamer populations to be determined by internal electronic and ster ic repulsions between the oxygen atoms. The results reported here provide a quantitative explanation of the conformational behavior of (1 -->6)-linked carbohydrates.