Modeling glycosaminoglycan-protein complexes

Glycosaminoglycans are long linear and complex polysaccharides that are fundamental components of the mammalian extracellular matrix. Therefore, it is crucial to appropriately characterize molecular structure, dynamics, and interactions of protein-glycosaminoglycans complexes for improving understanding of molecular mechanisms underlying GAG biological function. Nevertheless, this proved challenging experimentally, and theoretical techniques are beneficial to construct new hypotheses and aid the interpretation of experimental data. The scope of this mini-review is to summarize four specific aspects of the current theoretical approaches for investigating noncovalent protein-glycosaminoglycan complexes such as molecular docking, free binding energy calculations, modeling ion impact, and addressing the phenomena of multipose binding of glycosaminoglycans to proteins.