Anchoring Mode and Assembly of Influenza Haemagglutinin Fusion Peptides in Lipid Bilayers by MD Simulations.
The interactions of the fusion domain of influenza haemagglutinin (N-terminal
20 residues) and of synthetic fusion peptides with a POPC lipid bilayer have
been studied by Molecular Dynamics simulations. This domain is considered a
model system for studying processes occurring during viral membrane fusion. The
chosen sequences in the synthetic peptides correspond to fusogenic and
non-fusogenic mutants. Their different modes of anchoring/binding to the
membrane was analyzed. The N-terminal 11 residues of the fusion peptides are
helical and insert with a tilt angle with respect to the membrane plane of
30°, in agreement with experimental data. In general, fusogenic peptides
inserted more deeply into the bilayer, destabilising the lipidic chains.
Non-fusogenic mutants moved to the lipid/water interface and did not affect
significantly the calculated order parameters of the bilayer. These results
indicate a perturbed lipid packing upon fusogenic peptide insertion that could
facilitate membrane fusion. Finally, the stability of trimeric and hexameric
assemblies of fusogenic peptides was studied.