Combining mutual information with structural analysis to screen for functionally important residues in influenza hemagglutinin.

ABSTRACT: Influenza hemagglutinin mediates both cell-surface binding and cell entry by the virus. Mutations to hemagglutinin are thus critical in determining host species specificity and viral infectivity. Previous approaches have primarily considered point mutations and sequence conservation; here we develop a complementary approach using mutual information to examine concerted mutations. For hemagglutinin, several overlapping selective pressures can cause such concerted mutations, including the host immune response, ligand recognition and host specificity, and functional requirements for pH-induced activation and membrane fusion. Using sequence mutual information as a metric, we extracted clusters of concerted mutation sites and analyzed them in the context of crystallographic data. Comparison of

SUBMITTER: Kasson PM 

PROVIDER: S-EPMC2811693 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature