Computation of Hemagglutinin Free Energy Difference by the Confinement Method

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Abstract

Hemagglutinin (HA) mediates membrane fusion, a crucial step during influenza virus cell entry. How many HAs are needed for this process is still subject to debate. To aid in this discussion, the confinement free energy method was used to calculate the conformational free energy difference between the extended intermediate and postfusion state of HA. Special care was taken to comply with general guidelines for free energy calculations, thereby obtaining convergence and demonstrating reliability of the results. The energy that one HA trimer contributes to fusion was found to be 34.2 ± 3.4 kT, similar to known contributions from other fusion proteins. Although computationally expensive, the technique used is a promising tool for the further energetic characterization of fusion protein mechanisms. Knowledge of the energetic contributions per protein, and of conserved residues that are crucial for fusion, aids in the development of fusion inhibitors for antiviral drugs.

Original languageEnglish
Pages (from-to)11292-11303
JournalThe Journal of Physical Chemistry. B: Materials, Surfaces, Interfaces, & Biophysical
Volume121
Issue number50
DOIs
Publication statusPublished - 20-Nov-2017

Keywords

  • Journal Article
  • INFLUENZA-VIRUS HEMAGGLUTININ
  • VIRAL MEMBRANE-FUSION
  • MOLECULAR-DYNAMICS
  • IMPLICIT SOLVENT
  • VESICLE RELEASE
  • COILED-COIL
  • SIMULATIONS
  • PH
  • GLYCOPROTEIN
  • PEPTIDE

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