Multiscale modeling of glycosaminoglycan structure and dynamics: current methods and challenges

Glycosaminoglycans are long unbranched and complex polysaccharides that are an essential component of mammalian extracellular matrices. Characterization of their molecular structure, dynamics and interactions are essential to understand important biological phenomena in health and disease, and will lead to novel therapeutics and medical devices. However, this has proven to be a challenge experimentally and theoretical techniques are needed to develop new hypotheses, and interpret experiments. This review aims to examine the current theoretical (rather than experimental) methods used by researchers to investigate glycosaminoglycan structure, dynamics and interactions, from the monosaccharide to the macromolecular scale. It will consider techniques such as quantum mechanics, molecular mechanics, molecular dynamics, coarse graining and docking.