Molecular modeling of carbohydrates

The modeling of carbohydrates is undergoing rapid development. For example, the first comprehensive conformational mappings of disaccharides with flexible residues and the first molecular dynamics studies of carbohydrates have only recently been published. At the same time, interest in carbohydrates has been increasing dramatically, and there is a need for a publication that gently introduces the uninitiated and provides an overview of current research in the area. We feel that Computer Modeling ( Carbohydrate Molecules meets these needs. 

Fig. 51. — Space-filling, Molecular Model of the Oligomannoside Type of Carbohydrate Chain that Contains 9 Mannose Residues. [Numbers and letters correspond to the coding used in Figs. 50,53, and 54 (see also, footnote on page 221). The relatively close, spatial proximity of the A-Ds branch and the /V,A -diace tylchitobio.se core-region (2-1) is clearly illustrated.]...

S. Perez, C. Meyer and A. Imberty, Practical Tools for Molecular Modeling of Complex Carbohydrates and Their Interactions with Proteins. Mol. Engin., 5 (1995) 271. 

A. Imberty, K.D. Hardman, J.P. Carver and S. Perez, Molecular modelling of protein-carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A. Glycobiology, 1 (1991)631. 

Randell, K D, Frandsen, T P, Stoffer, B, Johnson, M A, Svensson, B, Pinto, B M, Synthesis and glycosidase inhibitory activity of 5-thioglucopyranosylamines. Molecular modeling of complexes with glucoamylase, Carbohydr. Res., 321, 143-156, 1999. 

For molecular modeling of the lipoproteins, values for the partial specific volumes of the lipoprotein components are required. The partial specific volume of an aqueous egg yolk lecithin suspension is 0.984 ml/g (Hauser and Irons, 1972), and this provides a reasonable approximation for the partial specific volume of the phospholipid occupying the surface monolayer of a lipoprotein. The reciprocal of the density of liquid triolein (Small, 1986) yields its partial specific volume, 1.102 ml/g, and provides a reasonable approximation for triglyceride dissolved in the cholesteryl ester-filled core of the LDL. For cholesterol, the partial specific volume of 1.021 ml/g measured in benzene (Haberland and Reynolds, 1973) has been employed. The value of 0.740 ml/g employed for the partial specific volume of apoBlOO was determined from its amino acid composition (Lee et al., 1987). A value of 0.60 ml/g was used for the partial specific volume of the carbohydrate moiety. One important parameter, the partial specific volume of cholesteryl ester, remains to be determined. As will be shown below, its value is estimated to be 1.058 ml/g. 

B. Coxon, Boat conformations Synthesis, NMR spectroscopy, and molecular modeling of methyl 2,6-anhydro-3-deoxy-3-phthalimido-a-D-mannopyranoside and its 15N-labeled analog, Carbohydr. Res., 322 (1999) 120-127. 

Coxon B, Sari N, Mulard LA, Kovac P, Pozsgay V, Glaudemans CPJ. Investigation by NMR spectroscopy and molecular modeling of the conformations of some modified disaccharide antigens for Shigella dysenter-iae type 1. J Carbohydr Chem 1997 16 927-946. 

A. Imberty, K. D. Hardman, J. P. Carver, and S. Perez, Glycobiology, 1,631 (1991). Molecular Modeling of Protein—Carbohydrate Interactions. Docking of Monosaccharides in the Binding Site on Concanavalin A. 

R 244 J.-R. Brisson and H.J. Jennings, NMR and Molecular Modeling of Complex Carbohydrates and Carbohydrate-Protein Interactions. Applications to Anti-Bacteria Vaccines , p. 543... 

White blood oells oontinually patrol the circulatory system and interstitial spaces, ready for mobilization at a site of trauma. The frontline scouts for leukocytes are carbohydrate groups on their surface called sialyl Lewis acids. When injury occurs, cells at the site of trauma display proteins, called selectins, that signal the site of injury and bind sialyl Lewis acids. Binding between selectins and the sialyl Lewis acids on the leukocytes causes adhesion of leukocytes at the affected area. Recruitment of leukocytes in this way is an important step in the inflammatory cascade. It is a necessary part of the healing process as well as part of our natural defense against infection. A molecular model of a sialyl Lewis acid is shown below, and its structural formula is given in Section 22.16. 

Chandrasekaran R. and Radha A. 1997. Molecular modeling of xanthan galactomannan interactions. Carbohydr Polym 32 201 208. 

Braccini, I., Grasso, R. P. Perez, S. (1999). Conformational and configurational features of acidic polysaccharides and their interactions with calcium ions a molecular modeling investigation. Carbohydrate Research, 317,119-130. 

The molecular recognition of septanose carbohydrates has been investigated in depth by using concanavalin A68 as a model lectin. Complex formation was analysed by STD experiments and showed the first direct evidence of binding, by a natural protein, for this class of ring-expanded carbohydrate molecules. 

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