Determining the orientation of protegrin-1 in DLPC bilayers using an implicit solvent-membrane model

Area of Science:

• Computational biophysics
• Molecular modeling
• Membrane biophysics

Background:

• Antimicrobial peptides (AMPs) are crucial for innate immunity.
• Understanding AMP interaction with lipid bilayers is key to their mechanism of action.
• Continuum models offer a promising approach to study these interactions.

Purpose of the Study:

• To predict the most probable orientation of the beta-hairpin antimicrobial peptide Protegrin-1 (PG-1) within DLPC lipid bilayers.
• To evaluate the capability of continuum approaches in determining peptide orientation.
• To compare computational predictions with experimental findings.

Main Methods:

• Utilized continuum models to represent solvent and lipid bilayer environments.
• Calculated transfer free energy for multiple PG-1 orientations from aqueous to membrane-water environments.
• Employed Poisson-Boltzmann equation for electrostatic contributions and surface area relationships for non-polar contributions.
• Determined the most favorable orientation based on the lowest relative transfer free energy.

Main Results:

• Continuum models successfully predicted the orientation of PG-1 in DLPC lipid bilayers.
• The most probable orientation for PG-1 was found to be oblique.
• The predicted tilt angle was approximately 19 degrees.

Conclusions:

• Continuum approaches are effective in predicting antimicrobial peptide orientation in lipid bilayers.
• The predicted oblique orientation of PG-1 aligns qualitatively with solid-state NMR experimental data.
• This study enhances the understanding of AMP-membrane interactions and mechanisms of action.