(773e) Study of Interaction and Transpassing of Human Beta Defensin-3 with Popg and Pops Membrane

Human beta defensin type 3 (hBD-3) is a cysteine rich small peptide. It has 45 residues and a charge density of +11. hBD-3 can form dimer or higher order oligomer. It has the potent antimicrobial activity even at high salt concentrations, which is believed to depend on its interaction with biological membrane. In this study, the interaction of hBD-3 dimer with 1 -Palmitoyl-2-oleoyl-sn-glycero-3 –phosphatidylserine (POPS) and 1 -Palmitoyl-2-oleoyl-sn-glycero-3 –phosphatidylglycerol (POPG) membrane bilayer is investigated using all- atom molecular dynamic simulation. Factors influencing the structure and dynamics of hBD-3 in lipids under different conditions are investigated, including altering-disulfide bonds between the cysteine residues of two hBD-3 monomers, protonation state of hBD-3, and NaCl concentration. Protonation and NaCl concentration does not influence notably the structure and dynamics of hBD-3 but hBD-3 structure is found to be more flexible in absence of disulfide bond. hBD-3 dimer showed a bit instability in POPS at protonated state other than that it was quite stable in both POPG and POPS in all conditions.

In order to understand the trans-passing process of hBD-3 dimer through the POPG/POPS lipid bilayer, the Potential Mean Force (PMF) is calculated using Umbrella Sampling method. Results are compared between different lipid bilayers.