Effects of toxin peptides PepA1 and PepA2 on human red blood cell membrane model: A molecular dynamics study

PepA1 and PepA2 are type I toxin peptides with similar amino acid sequences, and both these peptides inhibit Staphylococcus aureus intracellularly and are toxic to human red blood cells (RBCs). PepA2 is 10-fold more cytotoxic than PepA1. The present study investigated the effects of these two peptides on human RBC membrane by performing microsecond-level molecular dynamics simulations using the GROMACS software package. The results indicated that both toxin peptides distorted and destabilized the RBC membrane. At low concentrations, the peptides showed no significant difference in their effects on the cell membrane; however, at high concentrations, PepA2 induced more distortion and destabilization of the cell membrane than PepA1 and enhanced cell permeability, resulting in the diffusion of more water molecules through the membrane. Polar residues in PepA2 and hydrophobic residues in PepA1 mainly formed hydrogen bonds with the water molecules penetrating the membrane. PepA2 formed more alpha-helical structures and was more stable than PepA1, which may explain its strong toxicity. PepA2 also strongly interacted with the RBC membrane as compared to PepA1. The results of the present study could facilitate better understanding of the mechanisms of toxic peptides and assist in designing efficient antibacterial drugs.