(593d) Free Energy Calculation on Human Beta Defensin Translocation through Bacterial Lipid Membranes

Human beta defensin type 3 (hBD-3) is cationic cysteine rich small peptide. It belongs to the human innate immune system and has a broad-spectrum of antibacterial activities on bacteria, fungi, and viruses. It is believed that hBD-3 directly disrupts bacterial lipid membranes, breaks the cell membrane, thus to kill the cell. In order to understand the antibacterial mechanism of hBD-3, in this project, the translocation free energy of hBD-3 through both model Gram-positive and Gram-negative bacterial membranes were predicted. Since extensive sampling is extremely important to obtain accurate free energy barriers, which is only within reach for Coarse-Grained models, GROMACS coarse-grained molecular dynamics simulations using Martini forcefields were performed on hBD-3 crossing both model Gram-positive and Gram-negative bacterial membranes. In order to consider the concentration effect, hBD-3 in both monomer and dimer forms were studied. It was found that hBD-3 needs to overcome a lower energy barrier crossing Gram-positive bacterial membrane than Gram-negative bacterial membrane, and the higher the concentration, the lower the energy barrier. The simulation result supplies insight on the antimicrobial activities of hBD-3 translocating through bacteria.