title: Variable ligand- and receptor-binding hot spots in key strains of influenza neuraminidase.
abstract: Influenza A continues to be a major public health concern due to its ability to cause epidemic and pandemic disease outbreaks in humans. Computational investigations of structural dynamics of the major influenza glycoproteins, especially the neuraminidase (NA) enzyme, are able to provide key insights beyond what is currently accessible with standard experimental techniques. In particular, all-atom molecular dynamics simulations reveal the varying degrees of flexibility for such enzymes. Here we present an analysis of the relative flexibility of the ligand- and receptor-binding area of three key strains of influenza A: highly pathogenic H5N1, the 2009 pandemic H1N1, and a human N2 strain. Through computational solvent mapping, we investigate the various ligand- and receptor-binding "hot spots" that exist on the surface of NA which interacts with both sialic acid receptors on the host cells and antiviral drugs. This analysis suggests that the variable cavities found in the different strains and their corresponding capacities to bind ligand functional groups may play an important role in the ability of NA to form competent reaction encounter complexes with other species of interest, including antiviral drugs, sialic acid receptors on the host cell surface, and the hemagglutinin protein. Such considerations may be especially useful for the prediction of how such complexes form and with what binding capacity.
authors.forename: Lane
authors.initials: L
authors.lastname: Votapka
authors.forename: Ozlem
authors.initials: O
authors.lastname: Demir
authors.forename: Robert V
authors.initials: RV
authors.lastname: Swift
authors.forename: Ross C
authors.initials: RC
authors.lastname: Walker
authors.forename: Rommie E
authors.initials: RE
authors.lastname: Amaro