Molecular Dynamics Simulation Study of the Interaction of Piscidin 1 with DPPC Bilayers: Structure-Activity Relationship

To study structure-activity relationship of antimicrobial peptides and to design novel antimicrobial pep(ides with selectivity for bacterial cells, we have performed Molecular dynamics simulations of the interaction of Piscidin (Pis1) and its two analogues (Pis1-AA and Pis1-PG) with dipaimitoylphosphatidylcholine (DPPC) bilayer through 45 ns. Our results inform us of the detailed location and orientation of the peptide with respect to the bilayer as well as provide about hydrogen-bond-formation patterns and electrostatics interactions. Simulations show that Pis1 and Pis-AA form the most hydrogen bonds and Pis-PG forms the fewest hydrogen bonds with lipid. Thus, Pis1 and Pis-AA should have stronger interactions with the lipid head group when compared to Pis-PG. Experimental studies have shown that Pis1 and Pis1-AA have a high antimicrobial and hemolytic activities, and Pis1-PG has low hemolytic activity while keeps potent antimicrobial activity. Our results complement the previous experimental studies. According to our MD results and previous experimental studies, Pis1 and Pis1-AA are more effective at the zwitterionic bilayer comparing Pis1-PG. These properties of Pis1-PG could be accordance with its low hemolytic activities.