An ambitious and costly plan to churn out protein structures is shifting into its second phase, with the National Institutes of Health (NIH) announcing roughly $300 million in new awards today. Protein structures may shed light on how species are related and could pave the way for new drug targets. The project's ultimate goal is to deposit up to 5000 new structures in a public database by 2010.
The Protein Structure Initiative (PSI) launched as a pilot project 5 years ago with the goal of designing technologies that can rapidly deduce protein structures (Science, 11 March, 1554). Now it will divvy up roughly $200 million among four large-scale centers that, much like the centers that sequenced the human genome, will crank out protein structures as rapidly as possible. The rest of the money goes to six "specialized" centers that will focus on how to handle some of the most challenging proteins, including those that could become drug targets.
Deducing protein structures can quickly gobble even hefty amounts of cash, and awardees are trying to drive costs downward. "Our goal would be to get to less than $10,000 per protein," says Lance Stewart, vice president of the company DeCODE biostructures in Bainbridge Island, Washington, and the leader of one of the new specialized centers. Currently, he says, deducing structures of bacterial proteins can cost $100,000; more complex eukaryotic ones can soar to 10 times that.
Having deciphered structures for more than 1100 proteins, most of them bacterial, the Protein Structure Initiative is now looking to the "higher hanging fruit," says Director John Norvell of the National Institute of General Medical Sciences (NIGMS). Guy Montelione of Rutgers University, who directs the Northeast Structural Genomics Consortium, says his success rate for deducing eukaryotic protein structures is 1%, compared with 10% for bacteria, but he expects improved technologies, which the new money is helping fund, will boost his eukaryotic protein yield. His large-scale center will focus on protein networks in cancer biology, and he has ready lists of proteins that drive tumor growth.
But not everyone is happy with the plan. "I think it's unfortunate to spend such a large amount of money ... on getting structures rather than trying to inform function," says Thomas Steitz, a structural biologist at Yale University. He believes that a snapshot of a protein's structure, isolated from the other molecules with which it interacts, reveals little about its function, an issue that continues to generate debate in the structural biology world.
Protein Structure Initiative