Real World Experiences in Operating a Collaboratory: The Protein Data Bank Helen M. Berman Board of Governors Professor of Chemistry & Chemical Biology Director, Research Collaboratory for Structural Bioinformatics and the Protein Data Bank

What is the PDB? Single international repository for all information about the structure of large biological molecules Archival database with hundreds of thousands of users who depend on the data

Number of released entries Year

1970’s Grass roots community efforts to archive data Protein crystallographers discuss how to archive data June 1971 –Cold Spring Harbor meeting brings groups together (Cold Spring Harbor Symposia on Quantitative Biology, vol. XXXVI, 1972.) October 1971 –PDB is announced in Nature New Biology (7 structures; vol 233, 1971, page 223) 1975 –PDB receives first funding from NSF (~32 structures)

Nature New Biology CHAD

1980’s Technology takes off –molecular biology, instrumentation, computer hardware and software Structural biology is able to focus on medical problems Community efforts to promote data sharing IUCr guidelines requiring data deposition in the PDB are published

1990’s Number of structures increases exponentially Complexity of structures increases New databases begin to emerge More structures determined by cryo- electron microscopy Plans for structural genomics emerge User community for the PDB expands dramatically RCSB awarded contract for the PDB

Who does what? Rutgers –Data in: standards, validation, annotation UCSD/SDSC –Data out: search engine, Web site, data distribution

Communication VTC Electronic , forums, wikis Procedures Internal newsletter Retreats

Retreats Team building exercises Management training Technical discussions Time to get to know one another

VTC’s Two formal ones per week Ad hoc when there are issues to discuss

2000’s Continued growth in structure studies Structural genomics takes off RCSB PDB contract renewed 2bus Kurt Wüthrich, who determined the first first three-dimensional protein structure by NMR spectroscopy with coworkers (proteinase IIa inhibitor from bull seminal plasma) was awarded the Nobel Prize in Chemistry in 2002 Release of new database and website BMRB joins RCSB

The PDB is Global

Worldwide Protein Data Bank

Mission Maintain a single archive of macromolecular structural data that is freely and openly available to the global community

wwPDB Formalization of current working practice Members –RCSB PDB (Research Collaboratory for Structural Bioinformatics) –PDBj (Osaka University) –Macromolecular Structure Database (EBI) MOU signed July 1, 2003 Announced in Nature Structural Biology November 21, 2003

Guidelines and Responsibilities All members issue PDB ID’s and serve as distribution sites for data One member is the archive keeper (RCSB) All format documentation publicly available Strict rules for redistribution of PDB files All sites can create their own web sites

Future 60,000 structures by ,000 depositions per year in 2010 Complexity will increase dramatically New methods will yield new structures

Scientific Challenges Number of data files continues to increase Information content of each data file is increasing Many more very large macromolecular complexes New structure determination methods Structure genomics

Technical Challenges How do we represent diverse data? How do make a searchable database? How do we integrate with other data resources? How do we make a scalable system? How do we meet the needs of a diverse community?

“These studies should lead to an understanding of structure/function relationships and the ability to obtain structural models of all proteins identified by genomics. This project will require the determination of a large number of protein structures in a high-throughput mode.” Structural Genomics From the NIH Request for Proposals for Structure Genomics Centers: “The next step beyond the human genome project”

PSI - Structures (Sep images)

Community Depositors –Different methods: X-ray, NMR, cryo-EM Users –Specialists (structural biologists) –Generalists –Educators –Students –Lay community

Active Outreach Electronic Meetings Publications One on one Many workshops

Issues Standards: What is the role of the centers? What should it be? Long term preservation: How long? What are the options? Stability: Strong dependency of research community demands a more stable model

Bottom line All the interdependencies within wwPDB and between the scientific community and wwPDB call for a new funding model that will ensure the long term preservation and availability of the research data contained within these resources

Acknowledgements Operated by two members of the RCSB: Supported by: NIGMS The RCSB PDB is a member of the