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Finding a 'Holy Grail': simulated and experimental protein folding compares nicely

CHAMPAIGN, Ill. -- For years, the comparison of simulated and experimental protein folding kinetics has been a "Holy Grail" for biologists and chemists. But scientists seeking to confirm protein-folding theory with laboratory experiments have been unable to cross the microsecond barrier. This obstacle in time existed because experiments could not be performed fast enough, nor simulations run long enough, to permit a direct comparison.

Now, measurements from the University of Illinois at Urbana-Champaign and molecular dynamics simulations from Stanford University have at last been compared and found to be in very good agreement. A paper describing the work has been accepted for publication in the journal Nature, and was posted on its Web site www.nature.com/nature.

"By crossing the microsecond barrier, we can directly compare simulated and experimental protein folding dynamics, such as folding rates and equilibrium constants," said Martin Gruebele, an Illinois professor of chemistry, physics and biophysics.

To allow experiment and theory to meet on a microsecond time scale, the researchers designed a small protein based on the work of Barbara Imperiali and her colleagues, now at the Massachusetts Institute of Technology. Consisting of only 23 amino acids, the protein contains all three basic elements of secondary structure -- helices, beta sheets and loops -- but can fold simply and rapidly.

At Illinois, Gruebele and graduate student Houbi Nguyen measured folding times using a fast temperature jump experimental procedure. To initiate the folding and unfolding dynamics, the solution was heated rapidly by a single pulse from an infrared laser. As the proteins began twisting into their characteristic shapes, a series of pulses from an ultraviolet laser caused some of the amino acids to fluoresce, revealing to the researchers a time-sequence of folding and unfolding events from which the fol
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Contact: James E. Kloeppel
kloeppel@uiuc.edu
217-244-1073
University of Illinois at Urbana-Champaign
20-Oct-2002


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