Molecular Simulations of Human Beta Defensin 2 and 3 in Lipid Membrane

Abstract

Defensins are a family of potent antibiotics that are secreted by neutrophils, a type of white blood cell, and macrophages, cells that have the capability of engulfing foreign particles. Although the defensin family is diverse, this research primarily focuses on Human Beta Defensins (HBD) types 2 and 3. HBDs play a critical role in the human immune system, where they alert the immune system of foreign microbes, and repress fungi, bacteria and viruses. Recent studies suggest that HBDs can disrupt the bacterial membrane, causing cell leakage and resulting in bacterial cell death. To fully grasp the disrupting mechanism of HBD-2 and 3 on a bacterial cells' membrane, it is vital to study the structure and dynamics of HBDs in POPG lipid membrane. The POPG membrane typifies the negatively charged bacterial membrane. The result will shed light on possible new antibacterial drug design. Numerous form of simulation software are utilized in the presented research due to their distinct functions. Beginning with Charmm-gui to set up the initial simulation system, then running NAMD simulations with Charmm36 Force Field to generate trajectories, and finally monitoring the protein movements inside the lipid membrane via Virtual Molecular Dynamics. Using the trajectories generated from the simulation, the number of Hydrogen bonds and the interaction energy between defensin units and lipid membrane will be calculated. As well, the structure deviation from the initial structure will be calculated using Root Mean Squared Deviation (RMSD), and Root Mean Squared Fluctuation (RMSF).Defensins are a family of potent antibiotics that are secreted by neutrophils, a type of white blood cell, and macrophages, cells that have the capability of engulfing foreign particles. Although the defensin family is diverse, this research primarily focuses on Human Beta Defensins (HBD) types 2 and 3. HBDs play a critical role in the human immune system, where they alert the immune system of foreign microbes, and repress fungi, bacteria and viruses. Recent studies suggest that HBDs can disrupt the bacterial membrane, causing cell leakage and resulting in bacterial cell death. To fully grasp the disrupting mechanism of HBD-2 and 3 on a bacterial cells' membrane, it is vital to study the structure and dynamics of HBDs in POPG lipid membrane. The POPG membrane typifies the negatively charged bacterial membrane. The result will shed light on possible new antibacterial drug design. Numerous form of simulation software are utilized in the presented research due to their distinct functions. Beginning with Charmm-gui to set up the initial simulation system, then running NAMD simulations with Charmm36 Force Field to generate trajectories, and finally monitoring the protein movements inside the lipid membrane via Virtual Molecular Dynamics. Using the trajectories generated from the simulation, the number of Hydrogen bonds and the interaction energy between defensin units and lipid membrane will be calculated. As well, the structure deviation from the initial structure will be calculated using Root Mean Squared Deviation (RMSD), and Root Mean Squared Fluctuation (RMSF).