Receptor Binding by Influenza Virus: Using Computational Techniques to Extend Structural Data

Influenza attaches to host cells via hemagglutinin binding of cell-surface glycans. These relatively low-affinity interactions involving flexible ligands are critical in determining tissue and host specificity, but their dynamic nature complicates structural characterization of hemagglutinin-receptor complexes. Molecular simulation can assist in analyzing glycan and protein flexibility in crystallized complexes, assessing how binding might change under mutation or altered glycosylation patterns, and evaluating how soluble ligands may relate to physiological presentation on the plasma membrane. Molecular dynamics simulation also has the potential to help integrate structural and dynamic data sources. Here we review recent progress from analysis of molecular dynamics simulation and outline challenges for the future.