Perpustakaan Digital ITB

Human defensins are antimicrobial peptide produced by the innate host defense in response to the bacteria, fungi, viruses, and mycobacterium inva- sion. Human neutrophil peptides (HNPs) 1 and 2 are the most potent forms of human -defensins against the tested microbes in experimental researches. They can kill the pathogen through the membrane disruption mechanism. It is known that HNP1 and HNP2 show a commensurate potential against the gram-positive strain. However, HNP2 appeared to be more potent against the gram-negative bacteria than HNP1. The inner membrane of gram-negative bacteria contains phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) molecules as mixture lipids. In this study, we investigate the eect of HNP1 and HNP2 binding to the POPE/POPG mixed-lipid bilayers on the structure and stability of the protein and lipid, through the molecular dynam- ics simulation. We apply the wedge model for the membrane-bound structure, which suggests that the dimer inserts into the bilayer with the hydrophobic bottom contacting the hydrocarbon region of the membrane. The 3:1 lipid proportion of POPE and POPG is used as a model of the Escherichia coli membrane. We compare the microbial actions of HNP1 and HNP2 by analyz- ing the lipid structure changes due to the interaction between the hydrophobic residues of the peptide with the lipid tails. The membrane analyses show that the presence of HNPs has signicantly aect the lipid structure, shown by the decrease of area/lipid and the increase of the POPE/POPG bilayer thickness. However, the interaction of HNP1 with the membrane in the binding structure aects the lipid structure in nearly similar term to the interaction of HNP2 with the membrane.