Interaction between antimicrobial peptides and non-lipid components in the bacterial outer envelope

Antimicrobial peptides (AMPs) offer advantages over conventional antibiotics; for example, bacteria develop resistance to a lesser extent to AMPs than to small-molecule antibiotics. The interaction of the AMPs with the liposaccharide (LPS) layer of the gram-negative bacteria cell envelope is not well understood. I constructed a MARTINI model of a gram-negative bacterial outer membrane interacting with the AMP Magainin 2. In a 20 μs MD simulation, the AMP diffused to the LPS layer of the cell envelope and remained there, suggesting interactions between the Magainin 2 and the LPS layer causing the AMP to concentrate at that position. Furthermore, the free energy profile for the insertion of the Magainin 2 into the membrane was calculated using umbrella sampling, which showed that the AMP positioned such that the cationic sidechains of the AMP coordinated to the negatively charged phosphate groups of the LPS layer. These simulations indicate that AMPs partition into the LPS layer of a bacterial membrane