Solvent interactions determine carbohydrate conformation

Abstract

The relationship between the three-dimensional structures of oligosaccharides and polysaccharides and their biological properties has been the focus of many recent studies. The overall conformation of an oligosaccharide depends primarily on the orientation of the torsion angles (, , and ) between glycosyl residues. Numerous experimental studies have shown that in glucopyranosides the -torsion angle (O6-C6-C5-O5) displays a preference for gauche orientations, in disagreement with predictions based on gas-phase quantum mechanics calculations. In contrast, the -angle in galactopyranosides displays a high proportion of the anti-orientation. For oligosaccharides containing glycosidic linkages at the 6-position (136 linked), variations in rotamer population have a direct effect on the oligosaccharides' structure and function, and yet the physical origin of these conformational preferences remains unclear. Although it is generally recognized that the gauche effect in carbohydrates is a solvent-dependent phenomenon, the mechanism through which solvent induces the gauche preference is not understood. In the present work, quantum mechanics and solvated molecular dynamics calculations were performed on two representative carbohydrates, methyl ␣-D-glucopyranoside and methyl ␣-Dgalactopyranoside. We show that correct reproduction of the experimental rotamer distributions about the -angles is obtained only after explicit water is included in the molecular dynamics simulations. The primary role of the water appears to be to disrupt the hydrogen bonding within the carbohydrate, thereby allowing the rotamer populations to be determined by internal electronic and steric repulsions between the oxygen atoms. The results reported here provide a quantitative explanation of the conformational behavior of (136)-linked carbohydrates.T he phenomenon of carbohydrate recognition is critical to many biological functions, including the response of the immune system to bacterial pathogens, the attachment of viral inf luenza particles to host cells, and the hyperacute rejection of tissue transplants from nonhuman sources. Understanding the conformational properties of carbohydrates is essential for the elucidation of their mechanisms of action, which may aid in the design of carbohydrate-based vaccines, antiviral drugs, and other therapeutic agents. A significant amount of research has gone into the study of the three-dimensional structures and dynamics of oligosaccharides and polysaccharides for these reasons (1-18).Unlike polypeptides and proteins, oligosaccharides do not contain secondary-structural motifs and do not form wellorganized tertiary structures in solution. Rather, oligosaccharides often populate multiple conformational families, thus requiring both temporal and spatial descriptors to quantify their conformational properties. Experimental methods such as NMR spectroscopy and x-ray crystallography have a long history of application to carbohydrates. However, these methods generally result in a single three-dimensional model for th...

Understanding the bacterial polysaccharide antigenicity ofStreptococcus agalactiaeversusStreptococcus pneumoniae

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