PSI Production Phase Fact Sheet

PSI structure 

Exploring the protein structure universe

The Protein Structure Initiative (PSI), which ended in July 2015, was a national effort to assemble a large collection of protein structures in a high-throughput operation. Knowledge gained could help researchers better understand the function of proteins, learn how altered structures can contribute to disease and identify new targets for drug development.

Facts At a Glance

Goal: To use high-throughput methods developed during the PSI pilot phase for the production of a large number of unique protein structures and for the continued development of methods to improve the structural genomics pipeline; to remove bottlenecks to the protein expression, crystallization, production and structural determination of more challenging proteins, such as membrane proteins, small protein complexes and proteins from human and other higher eukaryotes.

Project period: July 2005 to June 2010

Total costs for 5 years: $325 million (funded largely by the National Institute of General Medical Sciences, with additional contributions from the former National Center for Research Resources)

Number of Centers: 14

  • 4 large-scale centers using high-throughput pipelines
  • 6 specialized centers developing new methods for solving more challenging structures
  • 2 homology modeling centers developing computational tools to predict structures from sequence
  • 1 resource center housing materials developed by PSI centers
  • 1 knowledgebase centralizing access to PSI data and other resources

Number of PSI-solved protein structures: 4,800 (as of August 2010)

Unique Structures (sharing less than 30 percent of their sequence with other known proteins): 4,100 (as of August 2010)

Selected Technical Highlights

  • Scientists at the Integrated Center for Structure and Function Innovation developed a high-throughput process to produce crystallization chaperones to help in crystallizing recalcitrant protein and RNA targets. The process can generate chaperones for 15-20 targets/month. Proceedings of the National Academy of Sciences. 2008 Jan 8; 105 (1): 82-7. Protein Science. 2008 Jul; 17(7): 1175-87.
  • Scientists at the Center for High-Throughput Structural Biology manipulated the metabolic pathways in yeast to reduce selenomethionine toxicity, a major impediment to using yeast as routine expression host to obtain protein targets for X-ray crystallography with anomalous dispersion phasing. Proceedings of the National Academy of Sciences. 2007 Apr 17; 104(16): 6678-83.
  • Cornell University scientists in the Center for High-Throughput Structural Biology developed a high-pressure cryocooling procedure that improves the diffraction quality of crystals cooled to reduce radiation damage during X-ray crystallography. The method eases or eliminates the complexity and uncertainty of using penetrative cryoprotectant chemicals. Acta Crystallographica. Section D, Biological Crystallography. 2007 May; 63(Pt5): 653-9.
  • Using a method that combines a small volume microcoil NMR probe and automated NMR data analysis, the Northeast Structural Genomics Consortium determined the complete 3D solution structure of a TRAM protein from Methanosarcina mazei. Collection times on a very small amount of protein (72 micrograms) in a small volume (6 microliters) were about twice those of conventional studies. Nature Methods. 2007 June; 4(6): 491-3.
  • The Accelerated Technologies Center for Gene to 3D Structure established proof of concept research toward the miniaturization and automation of in situ X-ray diffraction data collection from protein crystals using a simple microfluidic device that could be applied to high-throughput protein structure determination. Maneesh K. Yadav et al. In situ data collection and structure refinement for microcapillary protein crystallization. Journal of Applied Crystallography. 2005 Dec; 38: 900-905.
  • PSI-supported scientists at Lawrence Berkeley National Laboratory developed an automated crystal-mounting and alignment system that eliminates manual operations, reduces risk to fragile crystals, optimizes synchrotron beam time and facilitates advanced methods for the high-throughput collection of quality X-ray diffraction data. Structure. 2004 Apr; 12: 537-545. Acta Crystallographica. 2006 Aug; D62: 852-858.
  • Researchers at the Center for Eukaryotic Structural Genomics constructed models of X-ray crystallography target proteins for difficult cases where the experimental resolution is 2.5 Angstroms or worse by automatically fitting the structures of five amino acid segments extracted from the Protein Data Bank into the electron density. Bioinformatics. 2006 July; 22(14): e81-e89.

Read about other technologies being developed by the PSI centers on the technology portal of the PSI:Biology Structural Biology Knowledgebase.

For more information about the research centers, see the large-scale centers RFA, the specialized centers RFA and frequently asked questions about them.


NIGMS supports basic biomedical research that is the foundation for advances in the diagnosis, treatment and prevention of disease. NIGMS is part of the National Institutes of Health, U.S. Department of Health and Human Services. To learn more about NIGMS, visit

Content revised July 2015