Study of the Interactions of Human β Defensin Type 3 Protein with POPS and POPC Membrane

Abstract

Human β defensin type 3 (hBD-3) is a cysteine rich small peptide, which has 45 residues and a charge of +11. It can form dimer or higher order oligomer in solution. It has a broad spectrum of antimicrobial activities against virus, fungus, and both Gram-positive and Gram-negative bacteria even at high salt concentrations. Its antibacterial activity is believed to depend on its interaction with biological membrane. In order to understand the interaction mechanism of hBD-3 with lipid membrane, in this study, the interactions of hBD-3 dimer with 1 -Palmitoyl-2-oleoyl-sn-glycero-3 –phosphatidylserine (POPS) bilayer, which resembles negatively charged bacterial membrane and 1 -Palmitoyl-2-oleoyl-sn-glycero-3 –phosphatidylcholine (POPC) bilayer, which resembles neutrally charged human red blood cell membrane are investigated using all- atom molecular dynamics simulations. Inserting hBD-3 dimer into the center of the POPC lipid bilayer and POPS lipid bilayer, 55 ns all-atom molecular dynamics simulations were performed on each system. Analyzing the RMSD and RMSF on hBD-3 dimer, it is found that hBD-3 dimer is more flexible in POPS lipid bilayer than in POPC bilayer. Calculating the hydrogen bonds formed between hBD-3 dimer and lipids, hBD-3 dimer forms more hydrogen bonds with POPS lipid than with POPC lipid. The insertion of hBD-3 dimer into lipid bilayer causes membrane thinning, which is stronger in POPS lipids around the hBD-3 dimer than in POPC lipid bilayer. Besides that, it is found that almost same number of water molecules transpass through POPS and POPC lipid bilayer.