Bartusiak, Marcia F., Burke, Barbara, Chaikin, Andrew, Greenwood, Addison, Heppenheimer, T.A., Hoffman, Michelle, Holzman, David, Maggio, Elizabeth J., Moffat, Anne Simon. "10 Fold, Spindle, and Regulate: How Proteins Work." A Positron Named Priscilla: Scientific Discovery at the Frontier. Washington, DC: The National Academies Press, 1994.
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A Positron Named Priscilla: Scientific Discovery at the Frontier
FIGURE 10.8When experimenters replaced asparagine with valine, in the 16thamino acid position of the GCN4 leucine zipper, the result was a much stronger, more stable dimer than occurs naturally.
fastener, it takes for alpha helices to come together in trimers, instead of dimers. The results of experiments now under way will tell.
ANOTHER APPROACH IN THE QUEST FOR THE HOLY GRAIL
Despite the growing knowledge of the mechanics of lysozyme and leucine zippers, the Holy Grail of protein research, predicting structure from sequence, remains elusive. This was driven home to Harbury and his colleagues when, prior to synthesizing his experimental leucine zippers, he tried to predict what their structures would be. "Because the leucine zipper is such a tiny repetitive structure, Pehr could use effectively the most sophisticated methods for doing this calculation," says Alber. Nonetheless, "The calculation failed dramatically."
"We know the laws of chemical physics, so why can't we compute structure, given sequence?" David Eisenberg, professor of molecular biology at the University of California, Los Angeles, demands rhetorically. One cannot describe the folding of protein from first principles, he explains, because protein is too big and complex to be fitted into Schroedinger's equations, which are the mathematical expression of the chemical physics laws.
Another hypothetical approach would be to find the conformation with the greatest stability. Stabilities of different conformations can be calculated for small molecules, and, with certain exceptions, the conformation with the greatest stability is the correct one. The problem with this approach is that for proteins there are far too many potential conformations