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Talk-Guest Speaker-Liqun Zhang

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  • cmb seminar
When Dec 11, 2017
from 11:00 AM to 12:30 PM
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Molecular Dynamic Simulations on Human b Defensin Type 3


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 b 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. hBD-3 also has chemotactic activity by directly binding with chemokine receptors, and may even play a role in cancer progression.  In order to design novel antibiotics or agonist, it is important to understand the relationships between the structure, dynamics and functional mechanism of hBD-3.  


My talk will focus on the 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 intra-molecular disulfide bonds, which can restrain the structure of hBD-3. Those disulfide bonds can break in a specific pathway under the reducing condition, which was contributed mainly by entropy increase based on findings from our all atom molecular dynamics (MD) simulations.



Both Steered MD 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’s 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 higher ordered oligomer improves hBD-3’s antibacterial activity.

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