Molecular and energetic analysis of the interaction and specificity of Maximin 3 with lipid membranes: In vitro and in silico assessments

Abstract In this study, the interaction of antimicrobial peptide Maximin 3 (Max3) with three different lipid bilayer models was investigated to gain insight into its mechanism of action and membrane specificity. Bilayer perturbation assays using liposome calcein leakage dose–response curves revealed that Max3 is a selective membrane‐active peptide. Dynamic light scattering recordings suggest that the peptide incorporates into the liposomal structure without producing a detergent effect. Langmuir monolayer compression assays confirmed the membrane inserting capacity of the peptide. Attenuated total reflection‐Fourier transform infrared spectroscopy showed that the fingerprint signals of lipid phospholipid hydrophilic head groups and hydrophobic acyl chains are altered due to Max3‐membrane interaction. On the other hand, all‐atom molecular dynamics simulations (MDS) of the initial interaction with the membrane surface corroborated peptide‐membrane selectivity. Peptide transmembrane MDS shed light on how the peptide differentially modifies lipid bilayer properties. Molecular mechanics Poisson–Boltzmann surface area calculations revealed a specific electrostatic interaction fingerprint of the peptide for each membrane model with which they were tested. The data generated from the in silico approach could account for some of the differences observed experimentally in the activity and selectivity of Max3.