Glycan Builder for in Silico Glycosylation: Template-Based Structure Prediction of Carbohydrate Structures of Glycoconjugates

Abstract

Glycosylation is an important post-translational modification of proteins. Considerable efforts have been made to understand how glycosylation affects the structure, dynamics and function of proteins, but it remains an enigma due to the diversity and variability in the glycosylation. Primary sequences and the glycan composition on a glycosylation site can be identified using mass spectrometry and nuclear magnetic resonance spectroscopy, however, it is still a daunting task to obtain a crystal structure of a glycoconjugate with intact glycosylation. Here we present a web-based toolset, Glycan Builder, for in silico glycosylation of a protein. Previously, we have developed Glycan Reader, a web-based toolset for glycan modeling and simulation input generation, which allowed us to build a glycan structure database from PDB. The survey of carbohydrate structures in PDB shows that current PDB structures can cover many of the biologically relevant carbohydrates, particularly those used in glycosylation of protein. Test results on 43 glycoprotein structures demonstrates the template-based structure prediction method can reliably predict glycoconjugate carbohydrate structures. The toolset and database will be freely available through the web-based GlycanStructure portal (www.glycanstructure.org).