Molecular dynamics studies of the antimicrobial peptides piscidin 1 and its mutants with a DOPC lipid bilayer.

Piscidin 1 (Pis-1) has a high broad-spectrum activity against bacteria, fungi, and viruses but it also has a moderate hemolytic activities. To improve the antibacterial activity and to reduce toxicity, mutants Pis-1AA (G8A/G13A double mutant) and Pis-1PG (G8P mutant) have been designed based on the crystal structure of Pis-1. Eighteen independent molecular dynamics (MD) simulations of Pis-1 and its mutants with membranes are conducted in this article. Furthermore, 60 independent MD simulations of three peptides in water box have also been discussed for comparison. The results indicate that the unfolding process starts at the middle of the peptide. Pis-1 disrupts easily in the region of Val10-Lys14. Pis-1PG has a flexible N-terminal region, and the interaction between N-terminal and C-terminal is very weak. Pis-1AA has the most stable helical structure. In addition, percentage of native contacts and hydrogen bonds analysis are also performed. Lipid-peptide interaction analysis suggests that Pis-1 and Pis-1AA has a stronger interaction with the zwitterionic dioleoylphosphatidylcholine (DOPC) lipid bilayer than Pis-1PG. When compared with the results of peptide with membrane, peptides are unstable and unfolding quickly in water solution. Our results are applicable in examining diversities on hemolytic, antibacterial, and selectivity of antimicrobial peptides.