<br/>Glycosylation is an important posttranslational modification of proteins and plays a crucial role in protein efficacy. It also needs to be understood for optimization of recombinant protein expression. We study 3D structures of glycoprotein in atomistic detail starting from known crystal structures to examine the effect of oligosaccharides on glycoprotein structure to evaluate the accessibility of the oligosaccharide chains to glycan modifying enzymes. 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.<br/><br/>The particular class of proteins we are studying are so-called immunoadhesins, chimeric proteins combining the ligand-binding region of a cell receptor with the constant domain of an immunoglobulin.  These are promising candidates for therapeutics. These chimeric molecules form dimers through disulfide bonds and noncovalent interactions; this bivalency increases the affinity for the ligand. As examples we study an anthrax decoy protein as well as a ACE2-Fc chimera as which is a candidate for binding to the Sars-Cov2 spike protein.

Computational modeling of glycosylation of immunoadhesin proteins

ACS Fall 2020 Virtual Meeting

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