Abstract
Glycosaminoglycans (GAGs) play key roles in virtually all biologic responses through their interaction with proteins. A major challenge in understanding these roles is their massive structural complexity. Computational approaches are extremely useful in navigating this bottleneck and, in some cases, the only avenue to gain comprehensive insight. We discuss the state-of-the-art on computational approaches and present a flowchart to help answer most basic, and some advanced, questions on GAG-protein interactions. For example, firstly, does my protein bind to GAGs?; secondly, where does the GAG bind?; thirdly, does my protein preferentially recognize a particular GAG type?; fourthly, what is the most optimal GAG chain length?; fifthly, what is the structure of the most favored GAG sequence?; and finally, is my GAG-protein system 'specific', 'non-specific', or a combination of both? Recent advances show the field is now poised to enable a non-computational researcher perform advanced experiments through the availability of various tools and online servers.