GlycoSHIELD: an integrated approach toward structural glycobiology

Through the global endeavor to investigate the structure-function relationships of different Corona virus S proteins during the COVID-19 pandemic, we have numerous examples of how glycans actively maintain functional protein structures and how glycans passively shield protein surfaces to evade host immunity surveillance. We have observed a strong correlation between changes in glycosylation and protein functional dynamics; we have also gathered strong evidence of host receptor glycans being engaged in viral protein binding; glycosylation can also be targeted by our immune system. Nonetheless, the bona fide receptors of many viruses remain unknown; many reported host-pathogen interactions cannot be reproduced at the molecular level. While atomic insights into dynamic protein-glycan crosstalks can be investigated computationally, the required computing resources are prohibitively large for most researchers. To circumvent this, we have developed GlycoSHIELD to enable rapid simulations of glycan dynamics by grafting pre-computed ensembles of glycan conformers onto static protein structures. The resulting atomic models of glycoproteins agree surprisingly well with experimental observables, providing a vantage point to predict receptor and antibody binding sites. In this talk, I will discuss the development and possible applications of GlycoSHIELD and how it may help us annotate the functional importance of glycosylation in the context of host-pathogen recognition and immunity response, which is essential for improving our preparedness for next outbreaks of infectious diseases.

 

Key words: Corona virus, glycosylation, structural biology, CryoEM, mass spectrometry