TOPSAN – A community-driven resource for enhanced impact of structural genomics

data.Protein Structure Initiative "Bottlenecks" Workshop, NIH Campus, April 14-16, 2008

Biomedical theme: Central Machinery of Life -proteins conserved in all kingdoms of lifeBiological theme: Complete coverage of Thermotoga maritima

Srikrishna Subramanian

purificationexpressioncloning

struc. refinementstruc. validationannotationpublication

phasingdata collectionxtal screening tracing xtal mounting

crystallizationimagingharvesting

targetselection

PDB

• Joint Center for Structural Genomics• One of four large scale (production) centers of PSI2• ~ 600 structures deposited in the PDB• Sustained pace of ~15 PDB depositions per month

Structure determination is done on a semi-automated assembly line

Structure notes

We aim to describe every structure we determine.

- Introductionannotation, biology, function

- Results description of structure 2-3 figures (ribbon, active site) functional implications

- Materials and Methodsbrief protocol of all steps1 table (crystallographic stats)

- References

…but, structure determination far outpaces our publications…

PSI-1

PSI-2

Structure collage: PSIPublication statistics : http://olenka.med.virginia.edu/psi/

What are the reasons?• PSI rapidly solves structures of novel proteins

whose function we don't yet fully understand.• Structures are not usually associated with

extensive extant research literature. • Structures are not associated with ongoing

biochemical and biological research.• There cannot possibly be local expertise for all

proteins studied.

Knowledge Dissemination: The Digital Age

WEB 2.0 is reshaping how we share information:

Communities of globally distributed peers (Networks) built around rich, collaborative environments.

WikipediaCitizendiumScholarpediaGoogle Knols

TOPSANProteopediaPDBWikiOpenWetwareWikiomicsWikiProteins

Can we have the best of all worlds?

Peer-reviewed manuscript

Automated database annotationWiki/Community

Fast, reliable,scalable

Several existing databases/tools can assist experts to annotate protein structures.

Annotation:• Feeds from public databases• Expert-curated informationContent management:• Wiki-style editing (WYSIWYG editor)• Page-level access control• Structured fields + free text• Instant publication• Always open for comments and editsQuality control & authorship:• Encourage community collaboration• JCSG scientists & invited peers• Many authors - no contribution too

small• Lead authors (editors) in charge of

releases

TOPSAN content:

Protein Groups

Browsing Options

JCSG: Structures / Structure Notes / TOPSAN

300 of 614 JCSG structures have an annotation on TOPSAN

Building communities

Communities with specific biological interests

Structural coverage of T. maritima proteome

The biological community can utilize PSI structures only when they are aware of them

Functionally well characterized enzyme and is also a new fold.PDB ID: 3C8WTargetDB: 376561

Google sent us the largest number of visitors

UCSD & BurnhamBioinformatics CoreJohn WooleyAdam GodzikLukasz JaroszewskiSlawomir Grzechnik Sri Krishna SubramanianAndrew MorseTamara AstakhovaLian DuanPiotr KozbialDana WeekesNatasha SefcovicPrasad BurraJosie AlaoenCindy Cook

GNF & TSRICrystallomics CoreScott LesleyMark KnuthHeath KlockDennis CarltonThomas ClaytonKevin D. MurphyChristina TroutMarc DellerDaniel McMullan Polat Abdubek Claire AcostaLinda M. ColumbusJulie FeuerhelmJoanna C. HaleThamara JanaratneHope JohnsonEdward NigoghossianLinda OkachSebastian SudekAprilfawn WhiteYlva EliasGlen SpraggonBernhard GeierstangerSanjay AgarwallaCharlene ChoBi-Ying YehAnna GrzechnikJessica CansecoMimmi Brown

Scientific Advisory BoardSir Tom BlundellUniv. CambridgeHomme Hellinga

Duke University Medical CenterJames Naismith

The Scottish Structural Proteomics facility Univ. St. AndrewsJames Paulson

Consortium for Functional Glycomics,The Scripps Research Institute

Robert StroudCenter for Structure of Membrane Proteins,

Membrane Protein Expression Center, UCSF Soichi Wakatsuki

Photon Factory, KEK, JapanJames Wells

UC San FranciscoTodd Yeates

UCLA-DOE, Inst. for Genomics and Proteomics

TSRINMR CoreKurt Wüthrich Reto Horst Maggie JohnsonAmaranth ChatterjeeMichael GeraltWojtek AugustyniakPedro SerranoBill PedriniWilliam Placzek

TSRI Administrative CoreIan WilsonMarc ElsligerGye Won HanDavid MarcianoHenry TienLisa van Veen

Stanford /SSRLStructure Determination CoreKeith HodgsonAshley DeaconMitchell Miller Herbert AxelrodHsiu-Ju (Jessica) ChiuKevin JinChristopher RifeQingping XuSilvya OommachenHenry van den BedemScott TalafuseRonald ReyesAbhinav KumarChristine TrameDebanu Das

The JCSG is supported by the NIH Protein Structure Initiative (PSI) Grant U54 GM074898 from NIGMS (www.nigms.nih.gov).

Ex officio founding members Raymond Stevens , TSRI Susan Taylor, UCSD Peter Kuhn, SSRL/TSRI Duncan McRee, TSRI/Syrrx

JCSG Annual Meeting 2007