title: Structural basis for influence of viral glycans on ligand binding by influenza hemagglutinin.
abstract: Binding of cell surface glycans by influenza hemagglutinin controls viral attachment and infection of host cells. This binding is a three-way interaction between viral proteins, host glycans, and viral glycans; many structural details of this interaction have been difficult to resolve. Here, we use a series of 100-ns molecular dynamics simulations to further analyze available crystallographic data on hemagglutinin-ligand interactions. Based on our simulations, we predict that the viral glycans contact the host glycans within 1-2 residues of the ligand-binding site. We also predict that the glycan-glycan interactions contain both stabilizing and destabilizing components. These predictions suggest a structural means to explain why changes to viral glycosylation alter the efficiency and selectivity of ligand binding. We also predict that the proximity of these interactions to the ligand-binding pocket will impact the binding affinity of small glycomimetic ligands analogous to the influenza neuraminidase inhibitors currently in clinical use.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kasson
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D001665:Binding Sites; D002236:Carbohydrate Conformation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry; D008958:Models, Molecular; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011134:Polysaccharides; D019158:N-Acetylneuraminic Acid