Fig. 1: Schematic representation of the GlycoShape workflow (https://glycoshape.org).
Top: the GlycoShape GDB is a repository of glycan 3D structures from 1 ms cumulative sampling through uncorrelated replicas of deterministic MD simulations. Structures can be searched by drawing a structure according to the Symbol Nomenclature for Glycans (SNFG) with the integrated SugarDrawer tool83 or by searching by text in the International Union of Pure and Applied Chemistry (IUPAC), Web3 Unique Representation of Carbohydrate Structures (WURCS), Simplified Molecular Input Line Entry System (SMILES), GLYCAM and GlyTouCan formats. The GlyTouCan ID of the tetra-antennary complex N-glycan is shown in the example in blue. The successful search outputs general information on the glycan in the main tab and its 3D structure in the ‘Structure’ tab resulting from clustering analysis of the MD data with the populations (weights) corresponding to each cluster. This information can be downloaded in PDB, CHARMM and GLYCAM formats. Bottom right: Re-Glyco allows users to rebuild the 3D structures of glycoproteins to the desired glycoforms by sourcing 3D glycan structures from the GDB and to predict N-glycosylation sites occupancy through the bespoke GlcNAc Scanning tool. As an example shown here and discussed in Results, the CD16b from PDB 6EAQ (in blue) is processed through the GlcNAc Scanning tool, which correctly predicts occupancy of the sequons at N45 and N16251. These sites can be N-glycosylated with a ‘one-shot’ approach, where the same N-glycan structure is chosen to occupy all, as shown in the example, or manually with a site-by-site approach, where the user can select a different N-glycan structure at each site.
