Structural Studies on Protein Carbohydrate Interaction Using Molecular Modeling Techniques

Alongside the genome and proteins, carbohydrates constitute a third class of bioinformatic molecules. While the nutritional and structural roles of carbohydrates have long been understood, an appreciation of their function as information carriers and recognition molecules has occurred only recently. The protein-carbohydrate interactions have been investigated in recent years through the analysis of the 3-Dstructures of a number of proteins and their complexes with carbohydrates, by X-ray crystallographic and NMR methods as well as by molecular modeling studies. In the present work the nature of interactions between proteins and carbohydrates has been explored at the molecular level using advanced molecular modeling techniques. The first chapter provides a general introduction to the field of study highlighting the lectins from different sources, protein glycosylation and molecular modeling approaches for 3-D structure prediction. The second chapter presents the description of methods used in the present study. The third chapter presents the results and discussions on the prediction of 3-D structures of fucose-binding lectins (fucolectins) from different source, namely, animal, plant, bacteria and fungi using homology modeling techniques based on the crystal structures of fucolectins available in the database. A few newly published protein sequences have been selected from each group for structure prediction and analysis in order to understand their functional roles. Fucose and related sugars have been docked on to the carbohydrate-binding sites to get the structures of the complexes. The natures of chemical forces involved in sugar-protein interactions were analyzed to examine the strength of such binding. Influence of calcium ions on carbohydrate binding has also been explored wherever relevant. The validation of the modeling procedures are discussed in the last section of this chapter. The knowledge of these modeled structures and particularly of their carbohydrate recognition domains may provide valuable information in developing potent therapeutics. The fourth chapter presents some structural aspects of protein glycosylation at the asparagine residue (N-glycosylation)environment