Glyfinder and Glycoprotein Builder: Online Tools for Finding and Modeling Glycoproteins in the PDB

ABSTRACT

Tens of thousands of 3D structures of oligosaccharides have been deposited into the Protein Databank (PDB), representing hundreds of thousands of hours of effort by crystallographers. Yet, despite the critical importance of these structures in furthering the development of glycomimetic drugs, in explaining the activity of glycan-processing enzymes, and in providing a deeper understanding of the properties of glycoproteins and vaccines, they remain unnecessarily difficult to locate within the PDB. Part of this is due to limitations in searching for oligosaccharides on the PDB website, even after a recent carbohydrate remediation project completed by the PDB. While several databases have been reported that contain carbohydrate structural information extracted from the PDB, few offer flexible search capabilities and even fewer provide independent assessment of data quality. Here we present the GlyFinder and GlyProbity webtools (glycam.org/gf) and illustrate their application to locating oligosaccharides, carbohydrate derivatives, and glycoproteins stored in the PDB. We highlight the utility of curating the data on the basis of the theoretical conformational (CHI) energies [1] of the glycosidic linkages and illustrate how the deposited data can be employed to generate 3D models of glycoproteins, including the SARS-CoV-2 Spike protein [2].