Partitioning of Putative Antimicrobial Peptides Into a Model Bacterial Membrane: a Metadynamics Approach
摘要
Antimicrobial peptides (AMPs) are among the most promising candidates for solving the global health threat of bacterial multi-drug resistance. Despite the widely accepted understanding of their mechanism of action, prediction of AMP membrane penetration and translocation propensity remains a challenge. Here we employ a metadynamics approach to model the partitioning of ten recently identified peptides with putative antimicrobial activity into a model bacterial membrane. The peptides were isolated form the mucus of the garden snail Helix aspersa which has potent antibacterial, antiviral and anticancer properties. Our in silico experiments indicate that for three of the ten investigated peptides, a membrane translocation is energetically favorable. However, most peptides have deep and well-defined free energy minima within the lipid bilayer, hinting at an ability to insert themselves into the membrane, possibly through a gradual process.