Molecular dynamics (MD) simulations are widely used to model the 3D structure of glycoproteins, often to study the biological function of attached N-linked glycans, for example, in shielding pathogens from immune recognition and in modulating intercellular adhesion. While MD is a valuable tool to model the conformational ensemble of N-linked glycans convergence of the distribution of glycan orientations relative to the protein surface is difficult to achieve. Additionally, these simulations require expertise in biomolecular simulation and access to high-performance computing resources. To alleviate these barriers, modeling tools have been developed to rapidly model a conformational ensemble of glycans onto a protein surface. These methods ignore interactions between N-linked glycans and neighboring protein residues that can influence glycan orientation in solution. Here, we surveyed glycoprotein structures in the Protein Data Bank and employed in silico free energy calculations to quantify pairwise interactions between N-linked glycans and underlying protein residues. Identifying these stabilizing interactions can aid development of modeling strategies that better capture glycan–protein interactions.
