Protein Structure Initiative Mission Statement. The long- range goal of the Protein Structure Initiative is to make the three-dimensional atomic- level structures of most proteins easily obtainable from knowledge of their corresponding DNA sequences.
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Protein Structure Initiative Mission Statement. The long- range goal of the Protein Structure Initiative is to make the three- dimensional atomic-level.
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Protein Structure Initiative
Mission Statement. The long-range goal of the Protein Structure Initiative is to make the three-dimensional atomic-level structures of most proteins easily obtainable from knowledge of their corresponding DNA sequences.
Goals and Milestones
SubCommittee
Helen BermanDavid Eisenberg
Wayne Hendrickson Andrzej JoachimiakGaetano Montelione
George Phillips Janna Wehrle
Stephen Burley Ian Wilson
PSI Goals and Milestones Document
Integration of PSI activitiesand organization of metrics of progress
towards these goals is being done by the PSI Knowledge Base
Using Goals and Milestones Document as a guide, with input from other PSI Steering Committee sub-committees
Primary Goals of PSI2
Large-scale Protein Structure Determination3,000 Experimental Structures in PSI2
In addition to ~ 1300 in PSI1 4,300 totalLarge (BIG) and Very-large (Mega) Domain Families 70% effortBiomedical Targets 15% effortCommunity-nominated Targets 15% effort
Broad structural coverage of protein sequences leveraged by homology modeling
New Technologies and Infrastructure that accelerate the process and impact of 3D protein structure analysis
In PSI2 Yr 3, PSI provided 20% of Structures and ~60% of Novel Leverage of all US Structures Submitted to the PDB
In recent years, PSI Structures have ~ 6.5 - fold higher leverage/structure than nonSG Structures (i.e. ~ 100 models / structure)
Incremental coverage of UniProt since Jan 1, 2000 is 24%
PSI has provided 25% (6% / 24%) of the new coverage of UniProt since Jan 1, 2000
Structural Coverage has advanced significantly in the past 10 Years
PSI has made significant contributions
… but there is still a lot left to do…
Protein
Sequences
Biological Function
3D Structure
Deducing Biological Function from 3D Structure not a primary goal of
PSI2 project
SG Can Enable Biology
SG can target networks / biological processes while still addressing the PSI goals of structural coverage.
SG technologies can be applied to prokaryotic, eukaryotic, human, and viral proteins.
Structural similarity can provide clues to distant evolutionary relationships, and hypotheses regarding potential biochemical functions.
Nature and locations of bound ligands can provide clues to biochemical function and mechanisms.
PSI Knowledge Base and PSI Materials Repository provide information, protocols, and reagents which will provide the basis for traditional hypothesis-driven research projects.
Development of PSI - Biology
Sep 2007 PSI External Assessment
Jul 2008 Workshop on Homology Models for Biology
Jul 2008 PSI Directors Meeting
Sep 2008 PSI Directors White Paper
Oct 2008 Workshop on Visions for PSI3
Dec 2008 Recommendations of PSISteering Committee andAdvisory Committee
Development of PSI - Biology
Sep 2007 PSI External Assessment
Jul 2008 Workshop on Homology Models for Biology
Jul 2008 PSI Directors Meeting: Visions for PSI3
Sep 2008 PSI Directors White Paper
Oct 2008 Halloween Workshop: Visions for PSI3
Dec 2008 Recommendations of PSISteering Committee andAdvisory Committee
PSI Directors White Paper
Opportunities for Structural Genomics
Large Domain Families - BIG, MEGA
Metagenomics: Structural Genomics of Ecological Niches
Organisms or Organelles
Systems Biology and Networks
Pathways and Large Multiprotein Complexes
Detailed structure / function / dynamic analysis across protein families
Metagenomics
Blue Nodes NESG Structures
P53
p53
**
*
*
apoptosisTLR
IL21(JAK)
Bacterial FeS Cluster Assembly Operons
StructureElectrostatic
SurfaceConsurfSurface
ElectrostaticSurface
ConsurfSurface
B.subtilis IscU(NMR)
Kornhaber, Montelione
H.influenzae IscU(NMR)
Ramelot, Kennedy
S.pyogenes IscU(X-ray)Liu, Kim
E.coli SufE(X-ray)
Kuzin, Hunt
E.coli YgdK/SufE(NMR)
Liu, Szyperski
180°
Magenta - strongly conserved
Cyan - less conserved
Blue –positive charge
Red – negative charge
IscUs
YgdK / SufE
Evolution of Structure and Function
Development of PSI - Biology
Sep 2007 PSI External Assessment
Jul 2008 Workshop on Homology Models for Biology
Jul 2008 PSI Directors Meeting
Sep 2008 PSI Directors White Paper
Oct 2008 Holloween Workshop on Visions for PSI3
Dec 2008 Recommendations of PSISteering Committee andAdvisory Committee
Connecting with HTP Biology
The Network organization of PSI2 (OMG) is a model of how to organize large-scale biology project
Technology development, particularly for membrane proteins, should continue as a major component of PSI.
Can Structural Genomics Synergize with other HTP Omics Programs?