BMC Genomics 2009, 10(Suppl 3):S24 http://www.biomedcentral.com/1471-2164/10/S3/S24 Conclusion: The simulation results showed all hemagglutinin proteins used the same set of amino acid residues to bind with the glycoside; however, some mutations alter linkage preferences. Preference toward human-type receptors is associated with a positive torsion angle, while avian- type receptor preference is associated with a negative torsion angle. According to the conformation analysis of the bound receptors, we could predict the relative selectivity in accordance with in vitro experimental data when disaccharides receptor analogs were used. Background Avian influenza H5N1 virus uses its hemagglutinin (HA) protein to bind with a host receptor before entering the cell. This protein binds avidly to the avian-type receptor. However, a major health concern is that HA mutation could alter the binding preference to that of human receptor, which could occur before the virus is comple- tely adapted to its new host [1]. The incidences of human infection by H5N1 virus and the spectrum of H5N1 mutations are increasing [2-4]. Some of the mutated viruses could potentially infect humans and be spread person-to-person causing an outbreak [5,6]. The host cell selectivity of influenza A viruses is mediated by the interaction of particular viral HA variants to different host cell receptor types. The cell receptor that is bound by HA is a penta-saccharide chain. The first sugar unit is sialic acid (Sia), followed by galactose (Gal), N-acetylglucosamine (GlcNAc), Gal, and glucose (Glc) units. However, the available X-ray crystal structures of the host cell receptor are in the tri- saccharide form as shown in Figure 1, precluding accurate simulation of the full-length receptor. Two types of receptor are bound by influenza virus: the first type has the a(2,3)-linkage between the first two units to Figure 1 Receptor analog structures used in the molecular dynamics simulations. The left panel presents the defined torsion angle (F) of O6-C2-O3-C3 in the a(2,3) systems. The right panel presents the defined torsion angle of O6-C2-O6-C6 in the a(2,6) systems. Page 2 of 9 (page number not for citation purposes)