Antimicrobial peptide interactions with bacterial cell membranes.

Antimicrobial peptides (AMPs) are potential alternatives for common antibiotics because of their greater activity and efficiency against a broad range of viruses, bacteria, fungi, and parasites. In this project, two antimicrobial peptides including magainin 2 and protegrin 1 with α-helix and β-sheet secondary structures were selected to investigate their interactions with different lipid bilayers such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine (POPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), POPC/POPG (7:3), POPC/POPS (7:3), POPG/POPE(1:3), and POPG/POPE(3:1). The obtained structures of the AMPs illustrated that protegrin 1 cannot maintain its secondary structure in the solution phase in contrast to magainin 2. The head groups of the lipid units play a key role in the stability of the lipid bilayers. The head parts of the lipid membranes by increasing the internal H-bond contribute to membrane compactness. The POPG and POPS units inside the POPC/POPG and POPC/POPS membranes increase the order of the POPC units. The cationic residues of the AMPs form remarkable electrostatic interactions with the negatively charged membrane surfaces, which play a key role in the stabilization process of the peptide secondary structures. The Arg residues of protegrin 1 and the Gly1, Lys4, Lys10, Lys11, Lys14, and Glu19 of the magainin 2 have the most important roles in the complexation process. The values of Gibbs binding energies (ΔG) indicate that the complexation process between AMPs and different bacterial membranes is favorable from the thermodynamic viewpoint and AMPs could form stable complexes with the lipid bilayers. As a result of ΔG values, protegrin 1 forms a more stable complex with POPG/POPE(3:1), while the α-helix has more affinity to the POPG/POPE(1:3) bacterial membranes. Therefore, it can be considered that β-sheet and α-helix AMPs are more effective against gram-positive and gram-negative bacteria, respectively. The results of this study can provide useful details about the antimicrobial peptide interactions with the bacterial cell, which can be employed for designing new antimicrobial materials with greater efficiency.Communicated by Ramaswamy H. Sarma.