Protein therapeutics are an exceptionally valuable class of drug that typically have higher target specificity and potency than their small molecule counterparts. However, structural instability of protein therapeutics often plagues their pharmaceutical development. To ameliorate problems of chemical and physical instability both <i>in vitro</i> and <i>in vivo</i>, glycoengineering has been used to improve issues including proteolytic degradation, aggregation, and denaturation. To fully utilize the benefits of glycosylation in protein design, the effects of glycosylation on protein structure, and subsequent activity, need to be understood to such a degree that glycans can be rationally incorporated into glycosylation-naïve proteins. Although specific protein-sugar interactions are believed to intrinsically contribute to structural stability, a limited number of interactions between a particular sugar and amino acid have been fully investigated. Computational methods allow efficient examination of sequences with various combinations of different protein-sugar interactions. Since the Protein Data Bank contains over 3,400 glycoprotein structures, structural bioinformatics offers an effective starting point to systematically discern naturally occurring, high frequency patterns of protein-sugar interactions associated with a type of protein structure. Additional computational analyses of identified protein-sugar interactions are used to further investigate conclusions from structural bioinformatics. This molecular level knowledge of how sugars mediate protein structure can further our understanding of the intrinsic biophysical properties of glycoproteins and enable glycosylation to be used to engineer stable protein structures.

Elucidating an intrinsic role of glycosylation on protein secondary structure

251st National Meeting (2016)

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