( Rosetta@home lets public participate in...)Computers close in on protein structure prediction

Computers can predict the detailed structure of small proteins nearly as well as experimental methods, at least some of the time, according to new studies by Howard Hughes Medical Institute researchers.

The findings, which were reported in the September 16, 2005, issue of the journal Science, provide a glimmer of hope that scientists eventually may be able to determine the structure of proteins from their genomic sequences, a problem that has seemed insurmountable.

"For more than 40 years, people have known the amino acid sequence of a protein specifies its three-dimensional structure, but no one has been able to translate the sequence into an accurate structure," said senior author David Baker, an HHMI researcher at the University of Washington. "The reason this research is exciting is that we're showing progress in predicting the structure from the sequence. It's not that the problem is solved, but that there is hope."

Proteins are biological machines, and scientists need to determine their structures to understand how the proteins work. Now, scientists determine structures exclusively by measuring the atomic characteristics of proteins in the lab. In contrast, "in this case, we never touched a test tube," Baker said. "We gave it to a computer and said, 'go.'"

In the study, a sophisticated computer program folded 17 short strings of amino acids into 100,000 possible variations. When the researchers compared the best predictions to the actual structures solved earlier by other scientists using experimental techniques, they had the same success rate as the best hitters in major league baseball.

"We achieved almost atomic resolution in structure prediction for about one-third of our benchmark set of small proteins," said first author Philip Bradley, a postdoctoral fellow in Baker's lab. "It is a real step forward to achieve structures that are in some way comp
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Source:Howard Hughes Medical Institute