Glycans in silico: investigating conformational dynamics and interactions with proteins

Abstract

Carbohydrates (also called sugars or glycans) are omnipresent in the cells, along with proteins, nucleotides, and lipids. They constitute the basic building block of life. The role of glycans in metabolism and structural integrity has been considered for a long time. In addition, carbohydrates are present in various emerging classes of biomimetic materials. Glyco-nanomaterials are prospective building blocks for biosensors or multivalent scaffolds for drug delivery applications. Novel synthetic approaches and the rational design of carbohydrates and glycoconjugates have revealed new drug and vaccine discovery opportunities. However, despite the massive development of fascinating applications, carbohydrates remain the least structurally characterized among the major classes of biological molecules. Unlike proteins, nucleic acids, or lipids, carbohydrates are typically associated with a high extent of conformational heterogeneity resulting from the high number of monosaccharides and possible glycosidic linkages and also because of their intrinsic flexibility. Furthermore, glycans can be highly branched. Also, the biosynthesis of glycans is not dependent on any template, which creates a barrier to structure prediction. Consequently, carbohydrates arguably represent the most challenging class of biomolecules in terms of experimental characterization and elucidation of structure-function relationships. This opens a tremendous opportunity for the predictive application of computational methods such as molecular dynamics (MD) simulations to 3D structure predictions of glycans and revealing the binding mechanism of glycans to proteins.