Molecular dynamics simulations to understand glycosaminoglycan interactions in the free- and protein-bound states

Natural glycosaminoglycans (GAGs) are informational molecules with astounding structural diversity. Understanding the behavior of GAGs in the free and protein-bound states is critical for harnessing this diversity. Molecular dynamics (MD) offers atomistic insight into principles governing GAG recognition by proteins. Here, we discuss how MD can be used to understand local and global properties of GAGs in free solution, including torsions, puckering, hydrogen bonding, flexibility, and energetics. We discuss MD studies on GAG–protein complexes, which help elucidate the strength of interacting residues, role of water, energetics, and so on. The MD results accumulated so far suggest that GAG recognition of proteins is a continuum from the highly selective on one end to the fully non-selective on the other with intermediate levels of selectivity, including moderately selective and plastic. The advancements in MD technology, such as coarse-grained MD, coupled with really long simulations will help understand macroscale molecular movements in the future. •MD of GAGs offers atomistic details that are difficult to access using other methods.•MD of GAG – protein systems helps understand selectivity of recognition.•Recent advances position MD as a powerful approach to understand GAG biology.