Rapid Generation of a Representative Ensemble of N-Glycan Conformations

• Published in: In silico biology 2002, Vol.2 (3), p.427-439
• Main Authors: Frank, Martin, Bohne-Lang, Andreas, Wetter, Thomas, v.d. Lieth, Claus-W.
• Format: Article
• Language: English
• Subjects: Carbohydrate Conformation; Carbohydrate Sequence; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Monte Carlo Method; Polysaccharides - chemistry; X-Ray Diffraction
• ISSN: 1386-6338; 1434-3207
• DOI: 10.3233/ISB-00061

Glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces where their oligosaccharide moieties are implicated in a wide range of cellcell and cellmatrix recognition events. Glycans constitute highly flexible molecules. Only a small number of glycan X-ray structures is available for which sufficient electron density for an entire oligosaccharide chain has been observed. An unambiguous structure deter-mination based on NMR-derived geometric constraints alone is often not possible. Time consuming computational approaches such as Monte Carlo calculations and molecular dynamics simulations have been widely used to explore the conformational space accessible to complex carbohydrates. The generation of a comprehensive data base for N-glycan fragments based on long time molecular dynamics simulations is presented. The fragments are chosen in such a way that the effects of branched N-glycan structures are taken into account. The prediction database consti-tutes the basis of a procedure to generate a complete set of all possible conformations for a given N-glycan. The constructed conformations are ranked according to their energy content. The resulting conformations are in reason-able agreement with experimental data. A web interface has been established (http://www.dkfz.de/spec/glydict/), which enables to input any N-glycan of interest and to receive an ensemble of generated conformations within a few minutes.