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The Protein Structure Initiative ended 7/1/2015.
The long-range goal of the Protein Structure Initiative (PSI) is to make the three-dimensional atomic-level structures of most proteins easily obtainable from knowledge of their corresponding DNA sequences.
With the completion of the sequencing of the genomes of human and other organisms, attention has focused on the characterization and function of proteins, the products of genes. The availability of sequence data and the growing impact of structural biology on biomedical research have prompted scientific groups from several countries to undertake projects in the emerging field of structural genomics. Plans center on a coordinated international effort to determine protein structures on a large scale. The objective is to make these structures widely available for clinical and basic studies that will expand the knowledge of the role of proteins both in normal biological processes and in disease. The National Institute of General Medical Sciences (NIGMS) played a major role in the early planning for structural genomics and in 1999 organized a national program, the Protein Structure Initiative.
The PSI is accomplishing its goal by determining unique protein structures in a high-throughput mode of operation using X-ray crystallography and NMR spectroscopy to achieve a systematic sampling of major protein families and thus create a large collection of protein structures. These experimentally determined structures will be used as templates for computational modeling of related sequence homologs to produce structural coverage of a majority of sequenced genes.
During the pilot phase, major investments in technology and methodology development at the nine PSI research centers made each step of experimental structure determination more efficient, less expensive, and more likely to succeed. Specific goals included:
In the production phase, which began in 2005, the PSI evolved into an interacting network. Four large-scale research centers used the structural genomics pipeline to determine the structures of a selected fraction of proteins identified from analyses of gene sequences as targets for family representatives. The selected targets optimized structural coverage of sequenced genes. In addition, the relationships of structures to biological function and disease was explored. NIGMS is setting target selection policy for the PSI following discussions with advisors and the scientific community. In the future, the large-scale centers could also serve as centralized facilities capable of quickly providing structural information in response to critical biological and medical problems. Six specialized centers are focusing on technology and methodology development for high-throughput X-ray and NMR structure determination. Specific topics include protein production and crystallization of proteins that are not at present amenable to high-throughput approaches. Such proteins include membrane proteins, proteins that are in complexes, and human proteins. Two homology modeling center grants and a research project grant program are underway, focused on the improvement of computational methods of comparative modeling of protein structures. Additionally, a Materials Repository and Structural Genomics Knowledgebase have been established to provide the scientific community with access to protein expression clones and structural, functional, and experimental information generated by the PSI.
The overall goals of the production phase include:
As it grows, the PSI collection of structures is expected to have a significant impact on biological and medical research, in a similar way to the Human Genome Project. Expected benefits include the following:
This page last reviewed on
8/5/2015 9:40 AM
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