Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions.

Area of Science:

• Biophysics
• Computational Biology
• Membrane Biophysics

Background:

• Antimicrobial peptides (AMPs) like BP100 are crucial for innate immunity.
• The precise molecular mechanisms of AMP-induced membrane disruption remain incompletely understood.
• BP100 also functions as a cell-penetrating molecule carrier.

Purpose of the Study:

• To elucidate the initial molecular interactions between BP100 and model cell membranes.
• To understand the role of membrane charge and peptide conformation in AMP-membrane binding.
• To investigate the contributions of electrostatic and hydrophobic forces in AMP-membrane interactions.

Main Methods:

• Molecular dynamics simulations were employed to model the interaction of BP100 with zwitterionic and negatively charged lipid bilayers.
• Simulations analyzed peptide conformation, lipid aggregation, and binding forces at the membrane interface.
• Comparison with experimental data validated simulation findings.

Main Results:

• BP100 adopts an alpha-helical conformation upon binding to negatively charged membranes, consistent with experimental observations.
• The peptide initially binds via electrostatic interactions between its positive charges and anionic lipids.
• BP100 binding induced aggregation of anionic lipids on mixed lipid membranes.
• A subsequent flip of the peptide buries hydrophobic residues into the lipid bilayer.

Conclusions:

• The initial interaction of BP100 with membranes is governed by a combination of electrostatic attraction and the hydrophobic effect.
• The peptide's conformational change and subsequent insertion are critical steps in membrane disruption.
• These findings provide molecular-level insights into the mechanism of action for cationic antimicrobial peptides.