Dynamics of sialyl Lewisa in aqueous solution and prediction of the structure of the sialyl Lewisa–SelectinE complex

In this article we investigate all possible three-dimensional structures for sialyl Lewisa (SLea) in aqueous solution and we predict without a priori experimental information its conformation when bound to SelectinE by using a combination of long molecular dynamics (MD) simulations. Based on 10 ns MD studies, three structures differing in glycosidic conformations are proposed for SLea in aqueous solution. Based on a 4 ns MD study of the SLea–SelectinE complex with initial structures derived from our prediction tools, we find that, fucose and N-acetyl neuraminic acid are in close contact with SelectinE and therefore expect interactions of the protein with these two sugar rings to be significantly more important than in the case of galactose and N-acetyl glucosamine. Our predictions indicate that the N-acetyl glucosamine of SLea is positioned primarily in the aqueous phase. In order to be able to interact with SLea the side chains of amino acid residues Lys99 and Lys111 in SelectinE appear to undergo large conformational changes when contrasted with the positions of these residues in the X-ray crystal structure. Furthermore, amino acid residues Arg97, Glu98 and Lys99 are acting as a holding arm to position the NeuNAc of SLea in the binding pocket.