Glycobiology, 2000, Vol. 10, No. 3 329-338
© 2000 Oxford University Press
Glycosaminoglycan conformation: do aqueous molecular dynamics simulations agree with x-ray fiber diffraction?
School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
Glycosaminoglycan–protein interactions are biologically important and require an appreciation of glycan molecular shape in solution, which is presently unavailable. In previous studies we found strong similarity between aqueous molecular dynamics (MD) simulations and published x-ray diffraction refinements of hyaluronan. We have applied a similar approach here to chondroitin and dermatan, attempting to clarify some of the issues raised by the x-ray diffraction literature relating to chondroitin and dermatan sulfate. We predict that chondroitin has the same ß(1
4) linkage conformation as hyaluronan, and that their average ß(13) conformations differ. This is explained by changes in hydrogen-bonding across this linkage, resulting from its axial hydroxyl, causing a different sampling of left-handed helices in chondroitin (2.5- to 3.5-fold) as compared with hyaluronan (3.0- to 4.0-fold). Few right-handed helices, which lack intramolecular hydrogen-bonds, were sampled during our MD simulations. Thus, we propose that the 8-fold helix observed in chondroitin-6-sulfate, represented in the literature as an 83 helix (right-handed), though it has never been refined, is more likely to be 85 (left-handed) helix. Molecular dynamics simulations implied that 4C1 and 2SO, but not 1C4, forms of iduronate could be used in refinements of dermatan x-ray fiber diffraction patterns. Current models of 8-fold dermatan sulfate chains containing 4C1 iduronate refine to right-handed helices, which possess no intramolecular hydrogen-bonds. However, MD simulations predict that models containing 2SO iduronate could provide better (85 helix) starting structures for refinement. Thus, the 8-fold dermatan sulfate refinement (83 helix) could be in error.
1 To whom correspondence should be addressed at: Department of Chemistry, Carlsberg Research Centre, Gamle Carlsberg Vej 10, DK-2500, Valby, Copenhagen, Denmark