ALBUQUERQUE, N.M. -- That proteins fold isn't just a good idea, it's the law -- the law of life. Proteins are born resembling strings of beads. These fold to become brain, blood, biceps, and bone. But incomplete folds cause disabling diseases like Alzheimer's and "mad cow" syndrome. They also cause respiration and locomotion failures -- aims of biowarfare -- because protein functions can't be fully carried out.
Now the first successful computational model to capture the process of one protein interfering with the folding of another has been created at the Department of Energy's Sandia National Laboratories.
The results will help laboratory scientists understand the mechanisms by which incomplete folds occur, in order to prevent them.
"This is a step toward successful protein engineering," says principal researcher Sorin Istrail. "It provides our first clue in how to design sequences of laboratory proteins that can survive the essential but complicated folding process."
"Our next project is to apply our system to uncover clues about the mechanism of misfolding that occurs in Alzheimer's," he says.
Istrail collaborated with biologist Jonathan King and computer graduate student Russell Schwartz, both from the Massachusetts Institute of Technology. A paper describing the work will be published this spring in the Journal of Computational Biology (Vol. 6, No. 2).
Says King, "This is the first time any computer scientist has taken this fundamental step within a mathematically sound model. Though there are millions of proteins in any real-world experiment, the conceptual leap in modeling is in going from one protein to two."
King, president of the Biophysical Society, pioneered "wet" laboratory experiments to uncover protein-misfolding mechanisms.
The conceptual leap
The notorious complexity of simulating the folding of even a single protein, and the lack of computational resources to do so, had inhibited researchers from at
Contact: neal singer
DOE/Sandia National Laboratories