Structure and function

NIH initiative seeks to speed up the process of determining protein structures

Jeffrey Bouley
BETHESDA, Md.—Having established efficient pipelines for determining the three-dimensional shapes of proteins, the Protein Structure Initiative (PSI)—sponsored by the National Institutes of Health's National Institute of General Medical Sciences (NIGMS)—is now working to create new mechanisms for sharing the resources it has devel­oped, such as data and expression clones, with the scientific community.
 
The PSI, which began in 2000, is a ten-year ini­tiative, with the first five years spent developing methods, technologies, and pipelines to speed the structure production process and reduce its cost, according to Dr. Jeremy M. Berg, NIGMS director. The PSI funded a materials repository in September and next year will create an informa­tion hub where researchers can search for and submit structural information.
 
"The products of [our] efforts have been available to the scientific community, but the new resourc­es should dramatically enhance accessibility," he says.
 
The mission of the PSI, Berg explains, is to make protein structures available from protein sequences or gene sequences. Traditionally, he says, a lab work­ing on a small number of proteins might be able to determine three or four structures over the course of a year.
 
"So, from the point of view of drug discovery, if there is a particu­lar target that you are interested in, you are, as the PSI moves forward, more likely to have a model of a protein in the databank that you can use as a model to start think­ing about whether this is a good drug target," Berg says. "You may not find your protein specifical­ly, but you can get insights about potential binding sites."
 
"Because evolution reuses pro­tein shapes over and over, you're not confronted with the need to search out every protein encoded in the human genome to under­stand the function and struc­ture of human proteins," adds Stephen K. Burley, CSO of SGX Pharmaceuticals in San Diego and principal investigator of the New York Structural Genomics Research Consortium, which is one of the centers involved in the PSI.
 
A key aspect of the PSI, Berg notes, is that all the information is in the public domain, so structures are deposited within six weeks of when they are determined—typi­cally prior to being published in the literature—and are freely avail­able for any researcher to access.
 
Currently, the PSI has nearly 1,300 structures in the databank. The goal in phase two of the initia­tive is to add between 3,000 and 5,000 structures.

Jeffrey Bouley

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