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Powerful online tool for protein analysis provided pro bono by Stanford geneticist
Date:12/1/2008

ecule, from the standpoint of its biological activity, than on other, less-critical regions of that protein," Sidow said. If a change interferes with a protein's function, the hapless creature harboring this variant dies out; if not, the creature is fruitful and multiplies, and the variant protein persists in modern species.

It's by no means obvious just from looking at a protein's linear amino-acid sequence which regions are the "business districts" of the protein, and which are the sleepier bedroom communities. However, ProPhylER shows biologists which parts of a protein are key to its activity by comparing numerous versions of the same protein from different species. This is especially useful for proteins about which nothing or little is known, which is still the majority of proteins encoded in the human genome.

Human geneticists, too, will benefit from ProPhylER (a play on words derived from the bulkier term "PROtein PHYLogenetics and Evolutionary Rates"). Each of us carries tens of thousands of protein variants (due to mutations that have persisted in the human gene pool), some fraction of which affect protein function. For researchers, it is notoriously difficult to measure experimentally how much a protein's function is impaired by a mutation. ProPhylER provides specific predictions, also based on evolutionary variation, of the impact of a mutation on the protein's function. A mutation in an amino acid that has changed a lot in evolution is much less likely to be bad than a mutation that affects an amino acid in which evolution has not tolerated any change. "This type of analysis will be key in the interpretation of your personal genome sequence, when not if that becomes commonplace," said Sidow.

After a user has searched for his or her protein of interest, the ProPhylER Web site displays data via two interfaces. The first displays all the evolutionary data graphically along the length of the protein. The second, called "Crystal P
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Contact: Bruce Goldman
goldmanb@stanford.edu
650-725-2106
Stanford University Medical Center
Source:Eurekalert

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