Molecular Dynamics Simulations of Hemolytic Peptide δ-Lysin Interacting with a POPC Lipid Bilayer

Abstract

E-mail: leehs@uncw.eduReceived August 31, 2013, Accepted September 27, 2013The binding interaction between a hemolytic peptide -lysin and a zwitterionic lipid bilayer POPC wasinvestigated through a series of molecular dynamics (MD) simulations. -Lysin is a 26-residue, amphipathic, -helical peptide toxin secreted by Staphylococcus aureus . Unlike typical antimicrobial peptides, -lysin hasno net charge and it is often found in aggregated forms in solution even at low concentration. Our study showedthat only the monomer, not dimer, inserts into the bilayer interior. The monomer is preferentially attractedtoward the membrane with its hydrophilic side facing the bilayer surface. However, peptide insertion requiresthe opposite orientation where the hydrophobic side of peptide points toward the membrane interior. Suchorientation allows the charged residues, Lys and Asp, to have stable salt bridges with the lipid head-group whilethe hydrophobic residues are buried deeper in the hydrophobic lipid interior. Our simulations suggest thatbreaking these salt bridges is the key step for the monomer to be fully inserted into the center of lipid bilayerand, possibly, to translocate across the membrane. Key Words : -Lysin, Antimicrobial peptides, POPC bilayer, Molecular Dynamics (MD)IntroductionAntimicrobial peptides (AMPs)