tetano
Editor, Senior Moderator
J Am Chem Soc
. 2025 Apr 11.
doi: 10.1021/jacs.4c18441. Online ahead of print. Integrating Cryo-Electron Microscopy and Molecular Dynamics Simulations to Investigate Membrane Binding of Influenza Virus Fusion Peptides
Piotr Setny[SUP] 1 [/SUP], Paulina Borkowska[SUP] 2 [/SUP], Remigiusz Worch[SUP] 2 [/SUP]
Affiliations
We propose an approach for determining the positioning of membrane-active peptides within a lipid bilayer. It is based on a combination of cryogenic electron microscopy (cryo-EM) with molecular dynamics (MD) simulations. Cryo-EM image intensity profiles across peptide-containing liposome membranes are analyzed by comparing them to synthetic images that are derived from MD trajectories of peptide-membrane systems representing different assumed binding modes. These simulated profiles serve as baseline models, which are then used to classify experimentally obtained images into respective categories. The approach was applied to influenza virus fusion peptides, providing evidence for predominantly transmembrane binding in pure POPC membranes and a transition toward surface-bound configurations upon the addition of cholesterol.
. 2025 Apr 11.
doi: 10.1021/jacs.4c18441. Online ahead of print. Integrating Cryo-Electron Microscopy and Molecular Dynamics Simulations to Investigate Membrane Binding of Influenza Virus Fusion Peptides
Piotr Setny[SUP] 1 [/SUP], Paulina Borkowska[SUP] 2 [/SUP], Remigiusz Worch[SUP] 2 [/SUP]
Affiliations
- PMID: 40213862
- DOI: 10.1021/jacs.4c18441
We propose an approach for determining the positioning of membrane-active peptides within a lipid bilayer. It is based on a combination of cryogenic electron microscopy (cryo-EM) with molecular dynamics (MD) simulations. Cryo-EM image intensity profiles across peptide-containing liposome membranes are analyzed by comparing them to synthetic images that are derived from MD trajectories of peptide-membrane systems representing different assumed binding modes. These simulated profiles serve as baseline models, which are then used to classify experimentally obtained images into respective categories. The approach was applied to influenza virus fusion peptides, providing evidence for predominantly transmembrane binding in pure POPC membranes and a transition toward surface-bound configurations upon the addition of cholesterol.