Insight into the interactions, residue snorkeling, and membrane disordering potency of a single antimicrobial peptide...

Area of Science:

• Biophysics
• Biochemistry
• Computational Biology

Background:

• Antimicrobial peptides (AMPs) are crucial in innate immunity.
• Pardaxin, a membrane-active peptide, exhibits structure-dependent activity.
• Lipid bilayer composition significantly influences peptide-membrane interactions.

Purpose of the Study:

• To elucidate the molecular mechanisms of pardaxin interaction with diverse lipid bilayers.
• To investigate the structural dynamics, orientation, and residue behavior of pardaxin.
• To understand how lipid composition affects pardaxin's membrane activity.

Main Methods:

• All-atom molecular dynamics (MD) simulations.
• Modeling of pardaxin in six distinct lipid bilayer compositions (DMPC, DPPC, POPC, POPG, POPG/POPE 3:1, POPG/POPE 1:3).
• Analysis of peptide-membrane interactions, structural dynamics, and residue orientation.

Main Results:

• The C-terminal helix of pardaxin remained stable across all simulated bilayers.
• Pardaxin showed increased tilt into DMPC, DPPC, and POPG/POPE (1:3) bilayers compared to POPC and POPG.
• Zwitterionic membranes were more perturbed by pardaxin than anionic membranes.
• Cationic residues snorkeled towards the lipid bilayer interface.
• Phenylalanine residues were identified as critical for peptide-membrane interactions.

Conclusions:

• Lipid bilayer composition dictates pardaxin's structural dynamics and orientation.
• Pardaxin's interaction mechanism involves cationic residue snorkeling and phenylalanine involvement.
• This study provides molecular insights into antimicrobial peptide-membrane interactions.