The role of water in the design of glycosidic linkage flexibility

In this paper we show how a variety of computational methods are used to understand the role that water plays in the solution conformational dynamics of carbohydrates. A comparison is made between maltose and a designed disaccharide (α-D-Glc-NAc-(1→4)-β-D-Glc-3-NH2) in which the cross glycosidic linkage hydrogen bonds have been significantly strengthened. However, despite the stronger intramolecular hydrogen bonds in the maltose derivative, the correlation times for glycosidic dihedral angle fluctuations are approximately the same for the two sugars. Upon investigation of the water in the first hydration shells for the two disaccharides, high water probability densities were found between the functional groups straddling the glycosidic linkage that bonds the two monosaccharides together. This probability density corresponds to single water molecules forming bridging hydrogen bonds between the functional groups on either side of the linkage for periods of 3.66 ps in the case of maltose and 8.36 ps in the c...