Molecular insights into the differential membrane targeting of maximin 1 in prokaryotic and eukaryotic cells

Antimicrobial resistance is a pressing global health concern, underscoring the need for alternative treatments. Antimicrobial peptides (AMPs) have shown promise in this regard, with maximin 1 being a cationic, amphipathic AMP possessing antibacterial, antifungal, and antiviral activities with low hemolytic activity. In this study, we used molecular dynamics simulation to investigate the molecular basis for membrane selectivity of Maximin 1. By studying interactions between maximin 1 and different models of prokaryotic (anionic) and eukaryotic (zwitterionic) membranes, we found that Maximin 1 interacts more strongly with the prokaryotic membrane due to electrostatic attraction, while it weakly interacts with the zwitterionic eukaryotic membrane. Our simulations also revealed that Gly-1, Lys-5, Lys-11, Lys-15, and Lys-19 were identified to play a crucial role in the adsorption of maximin unto the prokaryotic membrane surface. The alpha-helical nature of the peptide, in addition to its amphipathic nature, was necessary for the adsorption of the peptide onto the surface of the prokaryotic membrane. Interestingly, the later transition of the alpha helix into a random coil was crucial in penetrating the prokaryotic membrane while hindering interactions with the eukaryotic membrane. Residues in the middle region of the peptide (residues 9-16) were also responsible for permeating the prokaryotic membrane over the eukaryotic membrane. These findings shed light on the peptide's selective targeting of bacterial membranes over human cell membranes and could inform the design of more effective AMPs.

Automated summary

This study used molecular dynamics simulation to investigate the membrane selectivity of antimicrobial peptide Maximin 1. The results showed that Maximin 1 interacts more strongly with the bacterial membrane due to electrostatic attraction and certain residues and structural characteristics play a crucial role in the adsorption and penetration of the bacterial membrane.