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Protein Structure Initiative


The Protein Structure Initiative (PSI) was a USA based project that aimed at accelerating discovery in structural genomics and contribute to understanding biological function. Funded by the U.S. National Institute of General Medical Sciences (NIGMS) between 2000 and 2015, its aim was to reduce the cost and time required to determine three-dimensional protein structures and to develop techniques for solving challenging problems in structural biology, including membrane proteins. Over a dozen research centers have been supported by the PSI for work in building and maintaining high-throughput structural genomics pipelines, developing computational protein structure prediction methods, organizing and disseminating information generated by the PSI, and applying high-throughput structure determination to study a broad range of important biological and biomedical problems.

The project has been organized into three separate phases. The first phase of the Protein Structure Initiative (PSI-1) spanned from 2000 to 2005, and was dedicated to demonstrating the feasibility of high-throughput structure determination, solving unique protein structures, and preparing for a subsequent production phase. The second phase, PSI-2, focused on implementing the high-throughput structure determination methods developed in PSI-1, as well as homology modeling and addressing bottlenecks like modeling membrane proteins. The third phase, PSI:Biology, began in 2010 and consisted of networks of investigators applying high-throughput structure determination to study a broad range of biological and biomedical problems. PSI program ended on 7/1/2015, even that some of the PSI centers continue structure determination supported by other funding mechanisms.

The first phase of the Protein Structure Initiative (PSI-1) lasted from June 2000 until September 2005, and had a budget of $270 million funded primarily by NIGMS with support from the National Institute of Allergy and Infectious Diseases. PSI-1 saw the establishment of nine pilot centers focusing on structural genomics studies of a range of organisms, including Arabidopsis thaliana, Caenorhabditis elegans and Mycobacterium tuberculosis. During this five-year period over 1,100 protein structures were determined, over 700 of which were classified as "unique" due to their < 30% sequence similarity with other known protein structures.


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