An Atomistic view of Short-chain Antimicrobial Biomimetic peptides in Action

Abstract

Amphiphilic {beta}-peptides, which are rationally designed synthetic oligomers, are established biomimetic alternatives of natural antimicrobial peptides. The ability of these biomimetic peptides to form helical amphiphilic conformation using small number of residues provides a greater synthetic advantage over the naturally occurring antimicrobial peptides, which is reflected in more potent antimicrobial activity of {beta}-peptides than its naturally occurring counterparts. Here we address whether the distinct molecular architecture of short-chain and rigid synthetic peptides compared to relatively long and flexible natural antimicrobial peptides translates to a distinct mechanistic action with membrane. By simulating the interaction of membrane with antimicrobial 10-residue {beta}-peptides at diverse range of concentrations we reveal spontaneous insertion of {beta}-peptides in the membrane interface at a low concentration and occurrence of partial water leakage in the membrane at a high concentration. Intriguingly, unlike prototypical natural antimicrobial peptides, the water molecules leaked inside the membrane by these biomimetic peptides do not span entire membrane, as supported by free energy analysis. As a major advancement, this work brings into lights the key distinction in the membrane-activity of short synthetic biomimetic oligomers relative to the natural long-chain antimicrobial peptides.