Background

 

Protein Structure Initiative (PSI):

The Protein Structure Initiative (PSI) is a federal, university, and industry effort aimed at dramatically reducing the costs and lessening the time it takes to determine a three-dimensional protein structure. The long-range goal of the PSI is to make the three-dimensional atomic-level structures of most proteins easily obtainable from knowledge of their corresponding DNA sequences.

Expected benefits from the PSI include: structural descriptions to help researchers discover the functions of proteins, design experiments, and solve other key biomedical problems; faster identification of promising new structure-based medicines; better therapeutics for treating both genetic and infectious diseases; and development of technology and methodology for protein production and crystallography.

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.

 

Protein Structure Initiative (PSI), NIGMS

 

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PSI Large-Scale Production Centers

NIGMS supports the following large-scape production centers in its Protein Structure Initiative:

PSI Specialized Centers

NIGMS supports the following specialized centers that will develop novel for quickly determining the structures of proteins that traditionally have been difficult to study:

  • Accelerated Technologies Center for Gene to 3D Structure (led by Lance Stewart, Ph.D., deCODE Biostructures, Bainbridge Island, Wash.)
  • Center for Eukaryotic Structural Genomics (led by John Markley, Ph.D., University of Wisconsin-Madison)
  • Center for High-Throughput Structural Biology (led by George De Titta, Ph.D., Hauptman-Woodward Medical Research Institute, Buffalo, N.Y.)
  • Center for Structures of Membrane Proteins (led by Robert Stroud, Ph.D., University of California, San Francisco)
  • Integrated Center for Structure and Function Innovation (led by Thomas Terwilliger, Ph.D., Los Alamos National Laboratory, Los Alamos, N.M.)
  • New York Consortium on Membrane Protein Structure (led by Wayne Hendrickson, Ph.D., New York Structural Biology Center, New York City)

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The Joint Center for Structural Genomics

This California-based center is developing high-throughput methods for protein production, crystallization, and structure determination. It will initially focus on novel structures from the roundworm Caenorhabditis elegans and on human proteins thought to be involved in cell signaling. It will also determine the structures of similar proteins from other organisms to ensure the inclusion of the greatest number of different protein folds.

Program Description

Organizations: The Scripps Research Institute, University of California at San Diego, Stanford University, Stanford Synchrotron Radiation Labs, Genomics Institute of the Novartis Research Foundation

Principal investigator: Ian Wilson, The Scripps Research Institute

Targets: Thermotoga maritima, mouse
Technology: crystallome screen of T. Maritima proteome; beamline automation; data centric informatics platform; nanovolume crystallization

Web site: http://www.jcsg.org

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The Midwest Center for Structural Genomics

This consortium of seven institutions is working to reduce the average cost of a protein structure from $100,000 to $20,000. The group will select protein targets from all three kingdoms of life (Eukarya, Archaea, and Bacteria), with an emphasis on previously unknown folds and on proteins from disease-causing organisms.

Program Description

Organizations: Argonne National Laboratory, Northwestern University, Washington University School of Medicine, University College London, University of Texas Southwestern Medical Center, University of Toronto, University of Virginia

Principal investigator: Andrzej Joachimiak, Argonne National Laboratory

Targets: microorganisms, especially pathogens

Technology: HTP target selection; automated gene cloning, protein expression, and solubility evaluation; low cost and high density fermentation; automated purification, crystallization, and structure determination; computational methods for fold analysis and function prediction; databases and LIMS

Web site: http://www.mcsg.anl.gov

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New York Structural GenomiX Research Consortium

Five institutions in and around New York City and San Diego, Calif., will develop techniques to streamline every step of structural genomics. The consortium expects to solve several hundred protein structures from humans and model organisms.

Program Description
Organizations: Structural GenomiX, Inc., Albert Einstein College of Medicine, Brookhaven National Laboratory, Columbia University, Rockefeller University, University of California at San Francisco, Weill Medical College of Cornell

Principal investigator: Stephen K. Burley, Structural GenomiX, Inc., San Diego, Calif.

Targets: disease related proteins from eukaryotes and bacteria

Technology: auto inducing media; His6-Smt3 protein expression vector; automation in protein production; automation in protein crystallization; automation in structure determination

Web site: http://www.nysgrc.org

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Northeast Structural Genomics Consortium

Researchers in New Jersey, New York, Connecticut, Washington State, and Ontario, Canada will target proteins from various model organisms--including the fruit fly, yeast, and the roundworm--and related human proteins. This consortium will use both X-ray crystallography and NMR spectroscopy to determine protein structures.

Program Description

Organizations: Rutgers University, Columbia University, Hauptman-Woodward Medical Research Institute, Ontario Cancer Institute, Pacific Northwest National Laboratory, State University of New York Buffalo, University of Toronto, Yale University, Weill Medical College of Cornell, Mt. Sinai School of Medicine

Principal investigator: Gaetano Montelione, Rutgers University

Targets: model eukaryotes -- D. melanogaster, S. cerevisiae, C. elegans, mouse, human

Technology: systemic bioinformatics on domain families; crystallization image analysis; NMR reduced dimensionality data collection; automated analysis of NMR structures

Web site: http://www.nesg.org

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