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Volume 2

Special Issue
GCB'01



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In Silico Biology 2, 0038 (2002); ©2002, Bioinformation Systems e.V.  



Rapid generation of a representative ensemble of N-glycans conformations

Martin Frank1, Andreas Bohne-Lang1, Thomas Wetter2 and Claus-W. v. d. Lieth1

1DKFZ (German Cancer Research Centre), Molecular Modelling, INF 280, 69120 Heidelberg, Germany
E-mail: a.bohne@dkfz.de, m.frank@dkfz.de, w.vonderlieth@dkfz.de
2University of Heidelberg, Medical Informatics, INF 400, 69120 Heidelberg, Germany
E-mail: thomas.wetter@med.uni-heidelberg.de


*Corresponding author


Edited by E. Wingender; received December 13, 2001; revised and accepted May 28, 2002; published June 19, 2002


Abstract

Glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces where their oligosaccharide moieties are implicated in a wide range of cell-cell and cell-matrix 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 determination 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 data base constitutes 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 reasonable 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.

Key words: conformations of N-glycans, molecular dynamics simulations, database of N-glycan fragments, glycoproteins