Structural Genomics

1
Structural Genomics
NIGMS Protein Structure Initiative

• Evolution has produced families of proteins with
  similar sequences and thus similar structures
• The structure of a representative of the family
  permits structure description of all family
  members by modeling
• Systematic and large-scale experimental effort to
  determine 10,000 selective structures in 10 years

2
Protein Structure Initiative (PSI)
NIGMS Protein Structure Initiative

• The NIGMS Protein Structure Initiative is a
  large-scale, high throughput effort to expand the
  determination of structures of unique proteins
  and leading to an inventory of protein structures
  in nature
• Research centers (P50)
• Research grants (R01, P01, SBIR, STTR)

3
P50 Research Centers
NIGMS Protein Structure Initiative

• Pilots to examine the best strategies for
  subsequent large-scale research networks
• Include all components of structural genomics
• Test computational approaches for coverage of all
  proteins in nature -- genome driven
• Test experimental tasks and development of high
  throughput methods increased efficiency lower
  costs
• Develop best management practices

4
NIGMS Requirements for P50s
NIGMS Protein Structure Initiative

• Timely deposition and release of coordinates in
  PDB after completion
• timely initially defined as 4-6 weeks
• Timely release of results and methodology
  development
• Development of publicly available website for
  protein targets, plans, progress, results, and
  methodology development

5
NIGMS Requirements for P50s
NIGMS Protein Structure Initiative

• Sharing of materials and samples
• Research training limited with justification
• Annual meetings
• Intellectual property protection is permitted,
  but subject to timely data release and coordinate
  deposition in the PDB

6
NIGMS Structural Genomics Research Centers
NIGMS Protein Structure Initiative

• New York SG Research Consortium, Stephen Burley
• SG of Pathogenic Protozoa Consortium, Wim Hol
• Midwest Center for SG, Andrzej Joachimiak
• Berkeley SG Center, Sung-Hou Kim

7
NIGMS Structural Genomics Research Centers
NIGMS Protein Structure Initiative

• Center for Eukaryotic SG, John Markley
• Northeast SG Consortium, Gaetano Montelione
• TB SG Consortium, Thomas Terwilliger
• Southeast Collaboratory for SG, Bi-Cheng Wang
• Joint Center for SG, Ian Wilson

8
Expectations of the PSI
NIGMS Protein Structure Initiative

• Inventory of protein structures and protein
  structure families
• unique, non-redundant proteins
• both known and unknown function
• public resource relate sequence to structure to
  function
• progress toward complete coverage of all protein
  structures found in nature

9
Expectations of the PSI
NIGMS Protein Structure Initiative

• Production level of 100 to 200 structures of
  unique proteins annually for each research center
  by the 5th year
• New high throughput methods -- benefits for all
  structural biology research and lower costs per
  structure
• Discovery of new protein folds

10
Recent Developments
NIGMS Protein Structure Initiative

• New PSI research center awards --
• Hol, Markley
• PSI Research Grants Program
• Target registration website (at PDB)
• Workshop on technical bottlenecks (Oct. 2001)

11
PSI Advisory Committee
NIGMS Protein Structure Initiative

• Brian Matthews (Chair), University of Oregon
• David Clayton, HHMI
• David Davies, NIDDK, NIH
• Chris Dobson, Cambridge University
• Ed Lattman, Johns Hopkins University
• Rowena Matthews, University of Michigan
• Frank Prendergast, Mayo Clinic
• Chris Sander, MIT

12
PSI Future Plans
NIGMS Protein Structure Initiative

• Workshops on protein production bottlenecks
  (March, 2002)
• Annual Meetings Scientific workshops, PIs, and
  PSIAC
• Bank for sharing materials -- reagents, crystals,
  clones (2003)

13
PSI Future Plans
NIGMS Protein Structure Initiative

• Electronic publications (2002)
• Experimental results publications/database (?)
• Communication, interaction, and cooperation
  between research centers (?)
• Large-scale research networks (2005)