 within influenza viral particles , the intricate balance between host cell binding and sialic acid receptor destruction is carefully maintained by the hemagglutinin ( ha ) and neuraminidase ( na ) glycoproteins , respectively . 
 a major outstanding question in influenza biology is the function of a secondary sialic acid binding site on the na enzyme . through a series of brownian dynamics ( bd ) simulations of the avian n1 , human pandemic n2 , and currently circulating pandemic ( h1)n1 enzymes , we have probed the role of this secondary sialic acid binding site in the avian n1 subtype . 
 our results suggest that electrostatic interactions at the secondary and primary sites in avian na may play a key role in the recognition process of the sialic acid receptors and catalytic efficiency of na . 
 this secondary site appears to facilitate the formation of complexes with the na protein and the sialic acid receptors , as well as provide ha activity to a lesser extent . 
 moreover , this site is able to steer inhibitor binding as well , albeit with reduced capacity in n1 , and may have potential implications for drug resistance or optimal inhibitor design . 
 although the secondary sialic acid binding site has previously been shown to be nonconserved in swine na strains , our investigations of the currently circulating pandemic h1n1 strain of swine origin appears to have retained some of the key features of the secondary sialic acid binding site . 
 our results indicate possible lowered ha activity for this secondary sialic acid site , which may be an important event in the emergence of the current pandemic strain . 
Supplementary Material