Theoretical insight into the relationship between the structures of antimicrobial peptides and their actions on bacterial membranes

J Phys Chem B. 2015 Jan 22;119(3):850-60. doi: 10.1021/jp505497k. Epub 2014 Aug 1.

Abstract

Antimicrobial peptides with diverse cationic charges, amphiphathicities, and secondary structures possess a variety of antimicrobial activities against bacteria, fungi, and other generalized targets. To illustrate the relationship between the structures of these peptide and their actions at microscopic level, we present systematic coarse-grained dissipative particle dynamics simulations of eight types of antimicrobial peptides with different secondary structures interacting with a lipid bilayer membrane. We find that the peptides use multiple mechanisms to exert their membrane-disruptive activities: A cationic charge is essential for the peptides to selectively target negatively charged bacterial membranes. This cationic charge is also responsible for promoting electroporation. A significant hydrophobic portion is necessary to disrupt the membrane through formation of a permeable pore or translocation. Alternatively, the secondary structure and the corresponding rigidity of the peptides determine the pore structure and the translocation pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacteria / cytology*
  • Bacteria / drug effects
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Lipid Bilayers / metabolism
  • Molecular Dynamics Simulation*
  • Molecular Sequence Data
  • Porosity
  • Protein Stability
  • Protein Structure, Secondary
  • Structure-Activity Relationship

Substances

  • Antimicrobial Cationic Peptides
  • Lipid Bilayers