Molecular Dynamic Simulations on Human Beta Defensin Type 3

Molecular Dynamic Simulations on Human Beta Defensin Type 3


  • Liqun Zhang, Tennessee Technological University, Cookeville
December 11, 2017 - 11:00am to 12:30pm


Defensins are cationic cysteine-rich small molecules with the molecular masses in the range of 3 to 5 kDa. They are a critical part of the innate immune system that provides an initial antimicrobial barrier for mucosal surfaces such as the surface of the eyes, airways, lungs, and skin. Human b defensins are mainly secreted by the epithelial cells, among which human beta defensin type 3 (hBD-3) is of special interest. It has a very high charge density (+11), and has antimicrobial activities against virus, fungus, and both gram-positive and gram-negative bacteria even at high salt concentrations, and may even play a role in cancer progression.

To design novel antibiotics or agonists, it is important to understand the relationships between the structure, dynamics, and functional mechanism of hBD-3. My talk will focus on oligomerization and the disulfide bonding status effect on its dynamics and function. hBD-3 can form a dimer or even higher ordered oligomer at high concentrations, which may further increase its functional activity, but its dimer structure is still unknown. My talk will introduce a simulation strategy to predict the defensin dimer structure. Besides that, hBD-3 has three pairs of intramolecular disulfide bonds, which can restrain the structure of hBD-3. The disulfide bonds can break in a specific pathway under the reducing condition. Steered molecular-dynamics and umbrella-sampling simulations were performed to find out if the oligomerization and the disulfide bonding status influence the antimicrobial capability of hBD-3. Based on the free energy calculation, it was found that the hBD-3 dimer has stronger translocation capability through a zwitterionic (but charge-neutral) lipid membrane than the monomer form, while breaking the disulfide bonds does no impair its translocation capability. That theoretically explains why forming a higher ordered oligomer improves hBD-3’s antibacterial activity.

Additional Information 

Please contact Lora Davis (574-6308, for building access.

Sponsoring Organization 

Center for Molecular Biophysics


  • Building: 2040
  • Room: Third-Floor Classroom

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