(593d) Free Energy Calculation on Human Beta Defensin Translocation through Bacterial Lipid Membranes
AIChE Annual Meeting
2021
2021 Annual Meeting
Engineering Sciences and Fundamentals
Thermodynamics at the Nanoscale
Thursday, November 11, 2021 - 8:54am to 9:08am
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.