About This ProjectPoisonous pesticides contaminate our environment and deadly nerve agents pose a threat to humanity. Our project is to re-engineer the bacterial enzyme phosphotriestease to break down these harmful chemicals in a safe and “green” way using state-of-the-art computer simulations to guide experimental methods.
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What is the context of this research?
The enzyme phosphotriesterase, or PTE, degrades the pesticide paraoxon. It has evolved from other enzymes to great efficiency over the course of only 50 years in response to the widespread agricultural use of organophosphate pesticides. Because many different pesticides also belong to the organophosphate class, PTE can breakdown many others such as chlorpyrifos and coumaphos. Many deadly nerve agents like sarin and VX gas also share a chemical make up similar to organophosphates and can be degraded into harmless byproducts by PTE. However, the breakdown of chemical substrates other than paraoxon is not very efficient. Using computer simulations we can customize and improve the specificity, stability, and efficiency of PTE.
What is the significance of this project?
Organophosphate pesticides have been contaminating the environment since the 1950’s. Enzymatic bioremediation using an engineered PTE should prove superior to other methods of removing toxins from soil and water.
Even though the use of most chemical weapons are banned by international law, they still pose a threat and many countries maintain stockpiles that need to be dealt with. PTE engineered to breakdown deadly nerve agents such as sarin, soman, and VX, could be used to safely dispose of these compounds. Additionally, an engineered PTE could potentially be used medicinally to treat nerve agent exposure in humans.
What are the goals of the project?
Our plan is to use Rosetta protein design methods, quantum mechanical methods, and experimental methods to achieve the following goals:
- Tailor the amino acid composition of the enzyme to favor binding to other substrates.
- Use both natural and non-canonical (synthetic) amino acids to improve enzyme stability.
- Improve the enzyme efficiency by altering the active site chemistry.
- Share the computer code and the enzymes with the world.
With funding, we can afford to order genes from companies like Blue Heron, rather than doing all the genetic manipulation in house. This will save time and increase the number of designs we can test greatly increasing our chances for success.
Meet the Team
Team BioI’m a PhD student in the Computational Biology program at New York University in the lab of Dr. Richard Bonneau. My training is in Computer Science (BS) and Molecular Biology (MS).
My interest in Computational Biology stemmed from the desire to harness the awesome power of nature's biomolecular machinery. Using computer modeling and simulations to guide experiments and designs, proteins and other macromolecules can be engineered to do work currently done with hazardous chemicals. Because proteins are biodegradable, designer proteins will provide industry with new capabilities without harming the natural environment.
I’m passionate about this project because it is a step toward protecting the planet and all that live here. It also involves some really impressive state-of-the-art technology!
When I’m not doing science I like to enjoy the outdoors and go camping and scuba diving any chance I get.
Nothing posted yet.
Rosetta docking of VX into the active site of PTE.
Rosetta is a macromolecular modeling software suite that is actively developed by a community of academic researchers all over the world. Originally developed for de novo protein structure prediction, it includes a variety of tools and methods for protein functional design, small molecule-protein docking, protein-protein docking, design using non-canonical amino acids, protein redesign for new functions, and many more. As one of our core tools, our lab regularly contributes to the Rosetta code base.
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