Investigation of the synergistic antimicrobial effect of Winter Flounder peptides using molecular dynamics simulations

With the fast-growing resistance of bacteria to antibiotics, antimicrobial peptides (AMPs) have gained attention as potential drug candidates because of their potency against a broad spectrum of bacteria. AMPs are ubiquitous in nature and their activity occurs through a wide range of mechanisms, including membrane disruption and immunomodulation. Although many AMPs have been tested in clinical trials, it has been observed that, in certain cases, the antimicrobial effect of combinations of AMPs is stronger than for each peptide alone. Analogous to combinations of drugs, combinations of AMPs could lead to more potent antibacterial agents with lower host toxicity, a delay in the evolution of drug resistance and a reduction in the dosage needed, hence causing less side effects. The use of molecular dynamics (MD) simulations has proven to be a powerful tool to investigate the molecular mechanisms which drive the antimicrobial effects of AMPs. Here we report the results of all-atom molecular dynamics simulations of the interaction of 10 different two-way combinations of Winter Flounder peptides, a family of cationic AMPs found in the epithelial mucous cells of winter flounder, against membrane models representative of gram-positive bacteria (100% POPG), gram-negative bacteria (POPE:POPG = 3:1) and red blood cells (RBC). The results of the MD simulations of the most promising WF peptides combinations in different bacterial membrane models could help shed light into the synergistic activity of AMPs and help guide the creation of effective AMPs cocktails for therapeutic use.