Interaction Between Antimicrobial Peptides and Non-lipid Components in Bacterial Outer Membrane

Antimicrobial peptides (AMPs) offer advantages over conventional antibiotics; for example, bacteria develop less resistance to AMPs. The interaction of the AMPs with the lipopolysaccharide layer of the gram-negative bacteria cell envelope is not well understood. This first interaction is essential for the peptide uptake and specificity to the target organism. In this work, we simulated the AMPs interactions with the bacterial envelope. We build a coarse-grained system formed by a gram-negative bacterial outer membrane, including the LPS layer and the AMP Magainin 2 using CHARMM-GUI Martini Maker. We perform 20us simulation on the free system using the molecular dynamics package GROMACS . During this simulation the AMP stays at 5nm in the Z axis, corresponding to the negative charge groups in the LPS layer of the cell envelope, this result suggests interactions between the positive charge of the Magainin 2 and the LPS layer. Finally, we calculated the Free Energy Profile for the insertion of the Magainin 2 in the membrane. For the Free Energy Profile construction, the AMP was restrained to 200 different positions across the membrane performing molecular dynamic simulation and to each window. The minimum of energy was found around the 4nm, suggesting an interaction between the AMP and the negative charge groups of the LPS layer of the bacterial cell envelope.