Designer Proteins

Proteins designed to follow marching orders are the latest in the new field of "synthetic biology," where scientists can create certain organisms to perform specific tasks. A new technology being developed by the Office of Naval Research and Duke University scientists would enable plants to change color in the presence of chemical and biological agents.

A new computational method for designing sensor proteins is the key. Plants that detect groundwater pollution around chemical facilities, for example, and react by changing color, could be feasible in the near future.

"A variety of uses are possible from this research," says Dr. Keith Ward, ONR project manager on the research. "This might include a glucose-sensing protein that could be used for monitoring diabetes, or a TNT-sensing protein to assist the U.S. Navy's underwater robots with locating and disarming explosion devices." At Duke University, with Dr. Homme W. Hellinga, associate professor of biochemistry at the University Medical Center in the lead, the newly redesigned proteins can detect everything from TNT to the neurotransmitter serotonin, which is thought to be a factor in some neurological disorders.

Research scientists began with the E. coli bacterium, whose perplasmic binding proteins act like Venus fly traps when they sense specific molecules that fit inside their hinged structures. "In other words, making a protein function is like having the right key to start a car. If you try to put a house key in the ignition, the car won't start. The same situation applies with proteins, where only the correct ligand will make the protein function properly," explains Ward. The goal of this research was to alter the proteins so that they could sense different molecules, such as TNT.

A new computational method makes the search for designer matches much easier. The scientists take the molecule they know they want the protein to bind to, such as TNT, and try trillions upon trillions of combinations of the different amino acids (building blocks of the protein) to see which would best bind to the TNT molecule. This is a data crunching process that can take up to several days. Once done however, scientists can then apply conventional techniques to alter the protein.

And they glow. In order to measure the sensing capabilities of the proteins, the scientists have attached a fluorescent molecule, called a fluorophore, to the protein that glows only when the target molecule has attached to the protein.

This science Tip-Off was written by ONR summer intern, Kate Haffey.