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- Why do cows turn mad - Modelling of prion protein folding and misfolding
 
Mad cow disease is one of the TSE diseases, which are believed to be caused by the isomerization and fibrillation of the prion protein (PrP) from its cellular form (PrPc) to its scrapie form (PrPsc). Such diseases affects brain or neural tissues and often times are fatal. It is found that glycosylation can affect the behaviors of such proteins. However, the reason is still a mystery. We are carrying out computer modelling to study how the glycosylatin affects the prion proteins.
The left is the human PrP monomer structure. Chitobiose glycans (in blue) are added to two glutamine residues, and the right is the same protein in the dimeric form. We have carried out simulations for them with and without glycosylations. It is found that chitobiose glycans have almost no effect on the monomeric protein. At the same time, the glycans will affect the dimer by stabilizing the β-sheet (in yellow) content, which is essential for the formation of PrPsc.
- From wood to ethanol - Study of cellulase catalytic mechanism by computer simulation
Cellobiohydrolase cellulase (CBH) is a family of proteins that break down cellulose (such as cell wall of plants) to its constituent monosaccharide (glucose) or disaccharide (cellobiose), which can be further fermented to ethanol. This provides a feasible method of converting biomass (tree and grass) into fuel. Although promising, the enzyme has its drawbacks. One of them is its low turnover rate. Researchers are looking into protein engineering, trying find a method to improve its performance.
Understanding the catalytic mechanism of this protein would provide a guide for protein modification. While the whole picture is not available at this moment, it is believed that the disruption of the crystalline cellulose substrate, followed by threading of the cellulose strand into the catalytic tunnel, is crucial for the reaction. Water molecules play important roles during this process. Computer modelling can provide atomistic-level understanding for such a mechanism. We are modelling the CBH1 from T. reesei with a large cellulose substrate in explicit solvent (not shown in the figure). Because of the size of the simulation, this research requires not only huge hardware resources (CPU time, hard disk and etc), but also software fine tuning for this specific system. This project involves multi-group collaboration including Cornell University, San Diego Supercomputer Center (SDSC) and National Renewable Energy Lab (NREL).
Our research will contribute to the understanding of ligocellulose, the ultimate goal of the Center for Lignocellulose Structure and Formation (CLSF), a DOE Energy Frontiers Research Center.
- Run a car with vegetable oil - Development of biodiesel process
Biodiesel, one of the alternative fuels, is produced from new or used vegetable oils, or even animal fats. In collaboration with Dr. Herzog, we are trying to adopt this technology to this campus. Our goal is to produce biodiesel fuel for vehicles on campus. By doing so, we hope to raise the awareness of alternative and clean energy resources that are not necessary hi-tech. We have already successfully converted unused vegetable oil into biodiesel in the lab. See here for what we do and what we get.
This undergraduate student research project won the 1st place award in the 2nd Mont Alto annual academic festival (2007). If any student is interested in participating in this exciting project, please contact me or Dr. Herzog.
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