Dynamics of the Influenza Hemagglutinin Fusion Peptide: A Comparison of MD and NMR

Abstract

Membrane insertion of influenza hemagglutinin (HA) is essential for viral membrane fusion. Previous NMR relaxation studies on bicelles [1, 2] analyzed the 23 conserved N-terminal residues of the HA2 subunit (fusion peptide). It was shown that this peptide, which adopted a helical hairpin structure, experiences wobbling motions relative to the bilayer surface on the ns timescale. Here, the dynamics of the HA fusion peptide hairpin on a DMPC membrane are studied using molecular dynamics (MD) simulations. Simulations were performed with the acidic groups (E11 and D19) protonated and unprotonated. Internal correlation functions of backbone N-H vectors are determined over the 100-ns MD simulations, and are fit to the Lipari-Szabo model free approach [3]. The calculated order parameters and correlation times are similar to those determined experimentally. Starting from an initial orientation parallel to the membrane, during the simulations the hairpin rotated nearly 90° around the axis that is parallel to the two helices, with the N-terminal helix buried more deeply in the lipid tail region.[1] J. L. Lorieau, J. M. Louis, and A. Bax, Proceedings of the National Academy of Sciences of the United States of America 107 (2010) 11341.[2] J. L. Lorieau, J. M. Louis, and A. Bax, Journal of the American Chemical Society 133 (2011) 14184.[3] G. Lipari and A. Szabo, Biophysical Journal 37 (1982) A380.