Computational Modeling of Therapeutic Glycoproteins

Glycosylation is an important posttranslational modification and plays a crucial role in protein efficacy. It is crucial to understand protein glycosylation in order to optimize recombinant protein expression. We study 3D structures of glycoproteins in atomistic detail starting from known crystal structures to examine how different glycosylation profiles can affect glycoprotein structure and function. Novel computational methods for modeling glycoprotein structures are employed to understand how changes in site-specific oligosaccharide composition and structure influence 3D glycoprotein structure, protein oligomerization, and product quality attributes such as activity/efficacy, stability, and immunogenicity. We are applying this methodology to a number of different proteins: Butyrylcholinesterase, a scavenger for organophosphorus nerve agents,; CMG2-Fc, a plant-made Fc-fusion anthrax decoy protein, and ACE2-Fc, a (plant-made) Fc-fusion protein that binds the Sars-Cov2 spike protein.