Implicit solvent model studies of the interactions of the influenza hemagglutinin fusion peptide with lipid bilayers

Dalit Bechor, Nir Ben-Tal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The "fusion peptide," a segment of ∼20 residues of the influenza hemagglutinin (HA), is necessary and sufficient for HA-induced membrane fusion. We used mean-field calculations of the free energy of peptide-membrane association (ΔGtot) to deduce the most probable orientation of the fusion peptide in the membrane. The main contributions to ΔGtot are probably from the electrostatic (ΔGel) and nonpolar (ΔGnp) components of the solvation free energy; these were calculated using continuum solvent models. The peptide was described in atomic detail and was modeled as an α-helix based on spectroscopic data. The membrane's hydrocarbon region was described as a structureless slab of nonpolar medium embedded in water. All the helix-membrane configurations, which were lower in ΔGtot than the isolated helix in the aqueous phase, were in the same (wide) basin in configurational space. In each, the helix was horizontally adsorbed at the water-bilayer interface with its principal axis parallel to the membrane plane, its hydrophobic face dissolved in the bilayer, and its polar face in the water. The associated ΔGtot value was ∼-8 to -10 kcal/mol (depending on the rotameric state of one of the phenylalanine residues). In contrast, the ΔGtot values associated with experimentally observed oblique orientations were found to be near zero, suggesting they are marginally stable at best. The theoretical model did not take into account the interactions of the polar headgroups with the peptide and peptide-induced membrane deformation effects. Either or both may overcompensate for the ΔGtot difference between the horizontal and oblique orientations.

Original languageEnglish
Pages (from-to)643-655
Number of pages13
JournalBiophysical Journal
Volume80
Issue number2
DOIs
StatePublished - 2001

Funding

FundersFunder number
Wolfson and Alon Foundations
Israel Science Foundation683/97-1

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