1. Protein Structure Initiative: Part 2
History
2000: Protein Structure Initiative begins
Goal: 10,000 structures in one decade
Progress (2005)
Many-fold price decrease
Increase in number of structures solved / year
But goal not quite in reach
With funding from the National Institutes of Health (NIH), the Protein Structure Initiative (PSI) was started in 2000 with the goal of determining the structures of 10,000 proteins. Earlier, researchers had determined that this number would sufficiently cover the universe of protein structures so that computer modeling could fill in the details. So far, the PSI has made significant strides in attaining this goal. In the first year of the program, it cost approximately $670,000 to solve a single structure. By the fourth year, that cost had fallen to only $180,000. Similarly, the number of structures solved by the PSI increased from 77 in the first year to 350 in the fourth year. The fifth year is estimated to yield roughly 500 structures. Despite this progress, it is unlikely that the PSI will be able to reach its goal of 10,000 structures by 2010, though many believe that between 4,000 and 6,000 three dimensional structures will be ready by then. The figure in the slide shows the increasing number of structures solved by the PSI as a percentage of the total number of new protein structures that are entered into the Protein Database (PDB) every year. By 2004, the PSI accounted for 42% of all unique structures entered into the PDB.
From Figure 2 in Service, R. (2005) “Structural Genomics, Round 2” Science 307:
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458

2. New challenges
Only 2-10% of proteins targeted by PSI centers become solved structures
Technology development vs. structure determination
Devote more resources to technology development
Means fewer structures solved in short term
Phase 2 of PSI
Anticipated decrease in budget
One of the greatest problems of structural genomics is achieving high-throughput. This issue arises from the fact that individual proteins often require tailor-made approaches for structural determination. At the present time, a PSI center is only able to solve the structures of 2-10% of the proteins it had originally targeted. This has raised a considerable amount of debate among those involved in the PSI, with some arguing that more funding should be dedicated to technology development. To complicate matters further, phase 2 of the PSI, which encompasses the next five years of progress, will likely receive less funding than the first five years due to current budgetary constraints.
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458