*2.3. Curated Information for Each GAG Entry*

For each entry, a detailed page is available, with 3D visualization, interactions, conformations, nomenclature, and links to external databases (Figure 3). The PDB code assigned to each entry is used to list alternative structures and to display additional information. Each structure is related to a protein with a UniProt accession number [49]. Each oligosaccharide is given a GlyTouCan identifier [60]. The 3D structures of the protein and the interacting GAG are visualized directly and interactively with LiteMol [61] and NGL Viewers [62]. High-resolution images of both the protein-GAG complex and the GAG are available for download. The atomic coordinates of the GAG, isolated from its interaction with the proteins, can also be downloaded for further use.

GAG-DB cross-references to several other databases that rely on a variety of strategies for visualizing the interaction between the GAG ligand and its protein environment (Figure 4). Several applications are available through the four different PDB sites, RSCG ORG, PDBe [51,53], PDBj [63], and PDB SUM [64].

**Figure 3.** Full results from the search on GAG oligosaccharide present in the database using 1FQ9 in the PDB field. More information can be obtained by clicking on the green bars.

**Figure 4.** Example of graphical representation of GAG binding site obtained from the PDBe ligand interface. Distribution of the amino acids involved in the binding to GAGs oligosaccharides in cocrystallized complexes. Illustration of two cases showing the hydrogen bonding and electrostatic interaction involved in the interaction. https://www.ebi.ac.uk/pdbe-site/pdbemotif/ ?tab=ligandbindingstats&ligandCode3letter1=IDS; https://www.ebi.ac.uk/pdbe-site/pdbemotif/?tab= ligandbindingstats&ligandCode3letter1=SGN.

Additional information on the interactions formed between the GAG and the protein can also be obtained using the protein-ligand interaction profiler (PLIP) server [50]. The NGL viewer [62] adapted to SwissModel [65] displays the interactions identified by the PLIP application that calculates and displays atomic level interactions (hydrogen bonds, hydrophobic, water bridge, etc.) occurring between GAGs and proteins. The specific features of the glycans interacting with the surrounding amino acid residues and possible metal ions are shown in 3D. The SwissModel application [65] provides direct access to the PDBsum deployed by the EMBL-EBI [64], CATH [66], and PLIP [50].

A cross-link to the PISA application [67,68] enables the exploration of quaternary structure formation and stability. The potential contribution of GAGs to the formation of quaternary macromolecular complexes requires the evaluation of energetic stability. The structural information relates to the interfaces between the macromolecular entities, the individual monomers, and the resulting assemblies, from which complex stability can be assessed or predicted. Supplementary Figures S1 and S2 provide examples of the interaction features offered by several visualization applications.
