LAUSR

Pleurocidin, a 25-residue cationic peptide, has antimicrobial activity against bacteria and fungi but exhibits very low hemolytic activity against human red blood cells (RBC). The peptide inserts into the bacterial membrane and causes the membrane to become permeable by either toroidal or carpet mechanism. Herein, to investigate the molecular basis for membrane selectivity of Pleurocidin, the interaction of the peptide with the different membrane models including the RBC, DOPC, DOPC/DOPG (3:1), POPE/POPG (3:1), and POPE/POPG (1:3) bilayers were studied by performing all-atom molecular dynamics (MD) simulation. The MD results indicated that the peptide interacted weakly with the neutral phospholipid bilayers (DOPC), whereas it made strong interactions with the negatively charged phospholipids. Pleurocidin maintained its α-helical structure during interactions with the anionic model membranes, but the peptide lost its secondary structure adjacent to the neutral model membranes. The results also revealed that the Trp-2, Phe-5, and Phe-6 residues, located in the N-terminal region of the peptide, played major roles in the insertion of the peptide into the model membranes. In addition, the peptide deeply inserted into the DOPC/DOPG membrane. The order analysis showed that Pleurocidin affected the order of anionic phospholipids more than zwitterionic phospholipids. The cholesterol molecules help the RBC membrane conserve integrity in response to Pleurocidin. This research has provided data on the Pleurocidin-membrane interactions and the reasons of resistance of eukaryotic membrane to the Pleurocidin at atomic details that are useful to develop potent AMPs targeting multidrug-resistant bacteria.