Abstract
Although a steadily increasing number of protein–ligand docking experiments have been performed successfully, there are only few studies concerning protein–sugar interactions. In this study, we investigate the interaction of wheat germ agglutinin (WGA) with N-acetylglucosamine and a number of its derivatives and predict the binding free energies using flexible docking techniques. To assess the quality of our predictions, we also determined those binding free energies experimentally in cell-binding studies. The predicted binding site, ligand orientation, and details of the binding mode are in perfect agreement with the known crystal structure of WGA with a sialoglycopeptide. Furthermore, we obtained an excellent linear correlation of our predicted binding free energies with both our own data and experimental data from the literature [Monsigny, M., Roche, A.C., Sene, C., Maget Dana, R. & Delmotte, F. (1980) Eur. J. Biochem.104, 147–153.]. In both cases, predicted energies were within 1.0 kJ·mol−1 of the experimental value. These results illustrate the usefulness of docking-based methods for the qualitative and quantitative prediction of protein–carbohydrate interactions. The insights gained from such theoretical studies may be used to complement the results from the still scarce crystal structures.