Carbohydrates: Second-class citizens in biomedicine and in bioinformatics?

Abstract

Carbohydrates differ from the two other classes of biological macromolecules (proteins and DNA) in two important characteristics: their residues can be linked by many different linkage types and they can be highly branched molecules. Carbohydrates contain a potential of information content which is several orders of magnitude higher in a short sequence than that of any other biological macromolecule. Carbohydrates on proteins can influence their properties and be involved in many biological recognition processes. Unlike peptides and proteins, oligosaccharides cannot yet be characterized in terms of their secondary structural or three-dimensional motifs, although it may be possible to develop a descriptive system. Certain specific conformations of the carbohydrates may play a key role for the recognition process. Various conformations of the carbohydrate ligands also influence the enzyme-substrate processing pathway. In addition, the inherent flexibility of many oligosaccharides in solution leads to structures that are frequently best described as ensembles of distinct conformations. Understanding conformational behaviour of carbohydrates is of cardinal importance and represents a challenge for theoretical conformational analysis techniques, such as systematic conformational search, molecular dynamics and Monte Carlo sampling.