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Published on: April 2, 2015
Conformational sampling of influenza fusion peptide in membrane bilayers as a function of termini and protonation
1Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
Abstract:
Influenza fusion peptide is critical for mediating the fusion of viral and host cell membranes during viral entry. The interaction of monomeric influenza fusion peptide with membranes is studied with replica exchange molecular dynamics simulations using a new implicit membrane model to effectively reach microsecond to millisecond time scales. The conformational sampling of the fusion peptide was studied as a function of different N- and C-termini, including an experimental construct with an additional C-terminal tag, as well as a function of protonation of acidic residues. It is found that the influenza fusion peptide mostly adopts helical structures with a pronounced kink at residues 11-13 with both N-terminal and C-terminal helices oriented mostly parallel to the membrane surface. A charged C-terminus and the presence of a charge C-terminal tag significantly alters the conformational sampling of the fusion peptide and results in more diverse conformational ensembles that include obliquely inserted N-terminal peptide structures. Protonation of acidic residues also affects the conformational sampling, however, based on pK(a) shift estimates the overall effect of pH = 5 on the conformational sampling of the influenza fusion peptide appears to be only minor.
Insights
Influenza fusion peptides adopt helical structures. Charged termini and tags alter peptide conformations, influencing viral entry mechanisms.
Area of Science:
- Biophysics
- Structural Biology
- Virology
Background:
- Influenza fusion peptide is essential for viral entry.
- Understanding its membrane interaction is key to inhibiting influenza.
Purpose of the Study:
- To investigate the conformational dynamics of influenza fusion peptide interacting with membranes.
- To explore the effects of termini modifications and protonation on peptide behavior.
Main Methods:
- Replica exchange molecular dynamics simulations.
- Utilized a novel implicit membrane model for extended timescale simulations.
- Analyzed conformational sampling based on N- and C-termini and residue protonation.
Main Results:
- Influenza fusion peptide predominantly forms helical structures with a kink.
- Charged C-termini and tags induce diverse conformations, including oblique insertion.
- Protonation of acidic residues has a minor impact on overall peptide conformation at pH 5.
Conclusions:
- Membrane-bound influenza fusion peptide conformation is sensitive to terminal charge and modifications.
- These findings provide insights into viral entry mechanisms and potential therapeutic targets.
