Boost to Crack Protein Structures

Structural biology just got a shot in the arm. The U.S. National Institute of General Medical Sciences (NIGMS) announced today that it has selected seven centers to be the initial test-beds for structural genomics, a field that aims to work out the structure of large numbers of proteins using robotics and advanced computers. The 5-year, $150 million program is intended to speed up the determination of three-dimensional, atomic-scale maps of proteins, which in turn should accelerate discovery of new drugs by giving pharmaceutical companies a closeup look at the proteins they are trying to target.

"This is a major undertaking," says Gaetano Montelione, a structural biologist at Rutgers University in New Jersey and leader of the Northeast Structural Genomics Consortium. "It's just a starting point for structural genomics. But it's a good start."

The program grew out of the widespread recognition that the Human Genome Project and similar gene-sequencing efforts are only the first step to understanding biology and disease. While genes harbor the cell's storehouse of genetic information, proteins carry out the bulk of cellular chemistry. Genetic sequences determine the order of amino acids in the proteins they code for, but the chainlike protein molecules generally fold into 3D shapes that cannot be predicted. Fortunately, proteins tend to cluster into families that share similar overall 3D shapes, or "folds." By finding examples of each of these folds, structural genomics researchers hope to identify patterns that will enable computer models to predict the shapes of unknown proteins from their amino acid sequences.

Officials at the National Institutes of Health say they hope the new program will enable them to determine the structure of as many as 10,000 proteins in the next 10 years. That's just a smattering of the more than 1 million proteins thought to be present in nature. Nevertheless, it would mark a surge in the pace of discovery for structural biologists, who have collectively solved the structures for only about 2000 unique proteins in the past 4 decades. It's also expected that the coming bolus of protein structures will reveal a large fraction of the estimated 1000 to 5000 protein folds thought to exist.

The centers, each a consortium of institutions ranging from universities and national labs to companies, are each slated to receive about $20 million over 5 years, a number that will vary depending on indirect costs paid to the institutions involved.

Related sites
The National Institute of General Medical Sciences
Northeast Structural Genomics Consortium
New York Structural Genomics Research Consortium
TB Structural Genomics Consortium
The Joint Center for Structural Genomics