(426b) The Hydrophobicity and Conformations of Common Glycosylation Motifs across the Kingdoms of Life

Post-translational modification of proteins occurs in organisms from all kingdoms life with glycosylation being among the most prevalent of amendments. The types of glycans attached differ greatly by organism but can be generally described as carbohydrate chains of variable lengths and degrees of branching constructed from many different monomers. With such diversity in structure, glycosylation serves numerous biological functions, including signaling, recognition, folding, and stability. While it is understood that glycans fulfill a variety important roles, structural and biochemical characterization of even common motifs and preferred rotamers is incomplete. To better understand glycan structure, particularly their relevance to protein stability, we modeled and computed the solvation free energy of 13 common N- and O-linked glycans in a variety of conformations using thermodynamic integration. N-linked glycans were modeled in the b-1,4-linked conformation, attached to an asparagine analog, while O-linked glycans were each modeled in both the α-1,4 and β-1,4-linked conformations attached to both serine and threonine analogs. Results indicate that both residue and linkage type have a significant effect on glycan solubility. Our results serve as a library of solvation free energies for fundamental glycan building blocks to enhance understanding of more complex protein-carbohydrate structures moving forward.