BERKELEY, CA- In a few seconds an origami artist can fold a sheet of paper into a bird or flower or pagoda or other intricate shape. In much less time a string of amino acids can fold itself into a protein, the kind of molecule that comes in many thousands of complex shapes and does most of the work of life. Origami can be taught, but no one knows how proteins fold themselves so quickly into the same shapes virtually every time.
Now, computer models devised by Daniel Rokhsar and his colleague Vijay Pande of the Department of Energy's Lawrence Berkeley National Laboratory, working at the National Energy Research Scientific Computing Center (NERSC), have revealed unexpected regularities in the pathways of protein-like structures. They report their findings in the Proceedings of the National Academy of Sciences, February 16, 1999 (vol. 96, no. 4). "We're interested in the physical mechanisms by which biomolecules achieve their structures," says Rokhsar, who is head of the Computational and Theoretical Biology Department in Berkeley Lab's Physical Biosciences Division and a professor of physics at the University of California at Berkeley.
The precise structure of biomolecules often reveals their functional secrets, a fact that became clear in the early 1950s when Linus Pauling solved the alpha-helix structure of keratin protein and Watson and Crick solved the double-helix structure of DNA.
Protein shapes determine everything from the texture of hair and horn to the catalytic coupling and uncoupling of innumerable enzymes essential to keep life's processes humming. Misfolded proteins can cause disease; in humans, sickle-cell disease and other anemias, for example, are caused by the misfolding of hemoglobin, whose normal structure, resembling a miniature spring-clip, allows it to capture, transport, and release oxygen in the bloodstream.
For any protein there is a "native state conformation," a thermodynamically
Contact: Paul Preuss
DOE/Lawrence Berkeley National Laboratory