biostudies-literatureUnknown95(7)Kasson PMBinding 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.Biophysical journalL48-50https://www.ebi.ac.uk/biostudies/studies/S-EPMC2547437biostudies-literatureStructural basis for influence of viral glycans on ligand binding by influenza hemagglutinin.PMC2547437Pande VSKasson PMfalseStructural basis for influence of viral glycans on ligand binding by influenza hemagglutinin.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.2008-01-01T00:00:00Z2008 Oct2021-02-21T05:58:27Z2019-03-26T22:31:50ZS-EPMC25474371864106810.1529/biophysj.108.141507