(377k) Molecular Simulation on Human Beta Defensin Type 3 Interaction with Lipid Membranes

by Christopher Elson

Advisor: Liqun Zhang

Defensins are cationic cysteine rich small molecules with molecular masses in the range of 3-5 kDa. They belong to the innate immune system. Mammalian defensins can be classified into α, β, and θ categories based on the disulfide bonding pattern. Human β defensin type 3 (hBD-3) is mainly secreted from the epithelial cells. It has antimicrobial activities by killing virus, fungus, both gram-positive and gram-negative bacteria even at high salt concentration. It is known that hBD-3 kills bacteria by directly interacting with the cell lipid membrane, but the molecular details including the structure characters are still unknown.

In this study, all-atom molecular dynamics simulations are performed to investigate how hBD-3 interacts with different kinds of lipid membranes. To achieve this goal hBD-3 is allowed to interact with both neutrally charged lipid bilayers such as POPC which represents the normal red blood cell membrane, negatively charged lipid bilayers such as POPS, and POPG which represent bacterial membranes. The initial systems were set up using CHARMM-GUI online program, and all-atom NAMD molecular dynamics simulations were conducted. VMD program has been applied to analyze the simulation trajectory. Approaching of hBD-3 to different kinds of bilayers has been observed. However, the binding between hBD-3 and POPS and POPG is much stronger than with POPC lipid bilayer. The result will help understanding the selectivity of hBD-3 interaction with different kinds of membranes, the binding dynamics and structure of the hBD-3 with lipid membrane, and will help designing optimum antibiotics in the future.