Berkeley Lab Research Review Winter 2000
  "Form follows function," said architect Louis Sullivan, arguing that a building's purpose should determine its design. If Sullivan had been a biologist he might have put it the other way around. With no designer except the rough and tumble of evolution, a protein's function is largely determined by its form; to find out what an unknown protein does, it's often essential to work out its shape.


Ever since James Watson and Francis Crick solved the double helix structure of dna in 1953, biology's most formidable structural challenge has been the "protein folding problem"-learning how nature gets from a gene, a length of dna that encodes the order of amino-acid residues in a string, to a working protein, that same string intricately folded into all the pockets and creases and knobs essential to the physics and chemistry of life.

While protein structures are being collected at a steadily increasing pace, knowledge of gene sequences is exploding. The Human Genome Project, begun by the Department of Energy and the National Institutes of Health less than ten years ago, will finish a draft of all 50,000 to 100,000 human genes-all three billion base-pairs-sometime this year. The majority of the proteins these myriad genes code for do not resemble any already known.

"The more information you have, the more kinds of information you need to make sense of it," says Daniel Rokhsar, head of the Computational and Theoretical Biology Department in the Lab's Physical Biosciences Division and a professor of physics at the University of California at Berkeley. "Without a simultaneous explosion in computation-powerful computers and flexible programs-we'll be overwhelmed."

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