Affiliations: DKFZ (German Cancer Research Centre), Molecular
Modelling, INF 280, 69120 Heidelberg, Germany E-mail: [email protected],
[email protected], [email protected] | University of Heidelberg, Medical Informatics, INF
400, 69120 Heidelberg, Germany E-mail:
[email protected]
Abstract: 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.
Keywords: conformations of N-glycans, molecular dynamics simulations, database of N-glycan fragments, glycoproteins
