Journal of Physical Chemistry B

Single mutation effects on conformational change and membrane deformation of influenza hemagglutinin fusion peptides

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The single mutation effect on the conformational change and membrane permeation of influenza hemagglutinin fusion peptides has been studied with molecular dynamics simulations. A total of seven peptides, including wild-type fusion peptide and its six single point mutants (G1E, G1S, G1V, G4V, E11A, and W14A, all with no fusion or hemifusion activity) are examined systematically, which covers a wide range of mutation sites as well as mutant residue types (both hydrophobic and hydrophilic). The wild-type shows a kink structure (inversed V-shape), which facilitates the interaction between the fusion peptide and the lipid bilayer, as well as the interaction between the two arms of the fusion peptide. All mutants show a strong tendency toward a linear aα-helix conformation, with the initial kink structure in the wild-type broken. More interestingly, one of the key hydrophobic residues around the initial kink region, Phe-9, is found to flip away from the membrane surface in most of these mutants. This conformational change causes a loss of key interactions between the original two arms of the inversed V-shape of the wild-type, thus disabling the kink structure, which results in the stabilization of the linear aα-helix structure. The fusion peptides also display significant impact on the membrane structure deformation. The thickness of the lipid bilayer surrounding the wild-type fusion peptide decreases significantly, which induces a positive curvature of lipid bilayer. All the single mutations examined here reduce this membrane structural deformation, supporting the fusion activity data from experiments. © 2010 American Chemical Society.


16 Jun 2010


Journal of Physical Chemistry B