www.wwpdb.org

1. www.wwpdb.org September 7, 2007

2. Agenda • Welcome and introductions • Accomplishments • Remediation rollout summary • Toward the future Break • Matters arising • Incorrect structures • Executive session • Feedback to wwPDB • Set next meeting date

3. wwPDB AchievementsOctober 2006 - September 2007 • Continued growth of archive • Website updates • Publications and presentations • Time-stamped archive • Remediation rollout • Annotation document • One stop shop: NMR, cryoEM

4. Depositions since wwPDB establishment

5. PDB entry processing • 1-1-2000 10,997 entries in PDB • Today 10-Jul-2007 44,578 entries in PDB Size now is 4 times larger than when the 3 sites started • In 1999, 2361 entries were deposited • In 2006, 7282 entries were deposited We handle more than 3 times as many entries per year with less staff – and all wwPDB sites produce high quality annotated PDB entries No current backlog of unprocessed entries

6. Time-stamped copies of the archive • 57 Gbytes of data for 2006, released January 2, 2007 • 68 Gbytes of data for July 2007 snapshot • Both include • PDB format entries • mmCIF format entries • PDBML format entries • Experimental data • Dictionary, schema, and format documentation

7. Outreach • wwPDB website • Discussion forums • NMR Task Force • Publications • Professional society meetings

9. Joint publications • Nucleic Acids Research, 35: D301 (2007) • The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data • Nature Structure Molecular Biology, 14:354 (2007) • Reply to: Building meaningful models of glycoproteins • Nature Biotechnology, 25: 854 (2007) • Response to “Overhauling the PDB” • Methods in Molecular Biology, in press • Data deposition and annotation at the wwPDB • Structural Bioinformatics 2nd Edition, in press • The wwPDB

10. Interactions since October 2006 • Exchange visits • MSD/RCSB PDB (4) • PDBj/RCSB PDB (1) • PDBj/BMRB (2) • BMRB/RCSB PDB (1) • Phone conference with site directors-twice a year • VTC’s among staff • BMRB/RCSB PDB twice a month (ADIT-NMR) • MSD/RCSB PDB twice a week (annotation procedures, remediation) • RCSB PDB/PDBj and BMRB/PDBj on necessary occasions • Email among staff • MSD/RCSB PDB ~2 per day • PDBj/RCSB PDB ~2 per day

11. New initiatives • One stop shop for NMR data and models • One stop shop for electron microscopy maps and models (NIH-funded)

12. Recommendations from 2006 wwPDBAC report • Implement the recommendations from November 19-20 2005 modeling workshop (Berman et al.Structure 14, 1211-1217) • Models phased out October 16, 2006 • Rollout remediated data to superusers by December 31, 2006; to all users by July 1st 2007; Provide access to PDB formatted files following the most current format. • Superusers had access to data November 2006, all users in April 2007

13. Recommendations from 2006 wwPDBAC report • Work with SAXS community to create appropriate representation of these data, and circulate progress reports to the Committee as appropriate • Not done • Expand the four character PDB ID codes before the number of depositions reaches 400,000 • Number of available PDB ID codes has been increased by allowing IDs to start with a character • Develop and present a formal recommendation to the wwPDBAC regarding the purview of the PDB at our September 2007 meeting in Princeton, NJ • In process

14. Recommendations from 2006 wwPDBAC report • Coordinate with the wwPDBAC to obtain formal letters of support when seeking funding; establish a coordinated plan to both educate and lobby funding agency representatives; establish a charitable organization to serve as a conduit for receipt of both grant funding and gifts from pharmaceutical and biotechnology companies, involving individual Committee members as needed. • Funding Representatives Round Table Discussion

15. Remediation

16. Key drivers • Chemistry and nomenclature • Sequence and taxonomy • Citations • Viruses

17. IUPAC, NMR, and the PDB Atom nomenclature and NMR restraints John L. Markley

18. History of the NMR-led requested remediation of hydrogen atom nomenclature • When BMRB was established in the late 1980’s, it adopted the IUPAC atom nomenclature recommendations from Biochemistry 9, 3471-3479, 1970 • At that time, we noted that NMR structures being deposited in the PDB did not adhere to these recommendations (particularly for H-atoms; e.g. HB1/HB2 instead of HB2/HB3), and I brought this to the attention of the director of the PDB at Brookhaven with the request that it be remedied • A group of NMR spectroscopists led by Kurt Wüthrich worked with the NMR community to develop recommendations for the deposition of NMR structures; all agreed that the prior IUPAC recommendations be maintained (Pure & Appl. Chem., 70, 117-142, 1998) • Over the years, wwPDB Task Force on NMR has pushed strongly for remediation of atom nomenclature

19. Accomplished: atom nomenclature remediation • Nomenclature in PDB now matches that in BMRB • The single format will avoid confusion and errors • All discrepancies have been resolved in the remediated files, with the minor exception of atoms at the C-terminus IUPAC-IUBMB-IUPAB wwPDB H'' HXT O' O O'' OXT • Since these atoms are not observed by NMR spectroscopists, we do not consider this to be a problem • We plan to write an addendum to the IUPAC-IUBMB-IUPAB “Recommendations” for submission to Pure & Appl. Chem. to formalize these as “accepted atom designators”

20. Remediation of NMR structure files • Required the linking of structure files and restraint files • Atom names, residue numbers and chain identifiers needed to be updated • Remediation of restraint files required the unpacking, parsing, and regularization of legacy information contained in PDB “MR” files into the “NMR Restraints Grid”

21. NMR Restraints Grid development BMRB, University of Wisconsin-Madison, USA MSD, European Bioinformatics Institute, Hinxton, UK Department of Computer Sciences/Condor Project, University of Wisconsin, USA Department of NMR Spectroscopy, Utrecht University, The Netherlands Centre for Molecular and Biomolecular Informatics, Radboud University, The Netherlands

22. NMR Restraints Grid development PDB MR files are converted into NMR-STAR NMR-STAR file and the corresponding PDB coordinate file are parsed; the information is connected inside the CCPN framework; and the results are written out as NMR-STAR files; converted restraint files are filtered to remove redundant restraints Files made available in the NMR Restraints Grid with access from links in each corresponding PDB entry NMR restraint data files with atom nomenclature corresponding to remediated PDB data files will be available by the end of 2007

23. Current state of the NMR Restraints Grid • Grid contains 3583 entries with a total of 3,882,595 parsed restraints • 3583 entries out of 6508 in PDB have restraints • Database is updated continuously as new PDB entries are released that have associated NMR restraints

24. Recent agenda items considered by the wwPDB NMR Task Force • Strongly recommend that restraints be mandatory for all NMR depositions to the PDB • Commissioned the development of procedures for representing uncertainty in NMR structures and for specifying the single model meant to be most representative of the structure • Task Force should write an article for J. Biomol. NMR on its recommendations for data representation and submission of experimental data • It was suggested that the Task Force begin to discuss validation issues

25. Most X-ray structures are supported by structure factors

26. Less than half of NMR structures are supported by restraint data

27. Most structural genomics centers regularly provide restraints, but the overall average is low Number of NMR structures deposited 247 Percent of deposited structures with restraints 1127 880 Structural genomics center

28. Remediation rollout Helen M. Berman

29. Remediation: scope and statistics • All primary citations verified (45K) • Sequences & taxonomy updated for 61K sequences • Ligand stereochemistry and nomenclature for 13M monomers and 170K non-polymer molecules • Symmetry and coordinate transformations for 280 virus entries • 10814 diffraction source & beamline updates • ~1000 miscellaneous uniformity issues

30. Remediation process • Corrections contributed and reviewed by all wwPDB members • Corrections on the archival mmCIF data files tracked in a version tracking system (CVS) • New PDBx/mmCIF, PDBML-XML, and PDB format data files produced • Validated by each wwPDB group • Staged public testing began January 2007 • Iterative corrections based on external comments made through July 2007 • Remediated archive released August 1, 2007

31. Remediation-supporting infrastructure • Internal (wwPDB) CVS archive remediation data files • Internal (wwPDB) rsync distribution site for remediated data files • Early tests of web, rsync, & ftp distribution sites for dictionaries, PDB, mmCIF, and XML data files • Complete wwPDB ftp site for remediated data and dictionaries updated with remediation corrections and weekly PDB updates • 200K CVS remediated data file updates • 1M+ remediated file updates to support testing and distribute from January 2007 - present

32. Checking the remediated files Haruki Nakamura

33. Different checks • References to external databases • Data processing consistency checks • PDBML/XML validation • Database loads • User-contributed diagnostics

34. References to external databases • Sequence and taxonomy (UniProt) • Primary Citations (PubMed)

35. Data processing consistency checks • Covalent geometry and stereochemistry • Compliance with wwPDB Chemical Component Dictionary • Molecular and stereochemical assignment • Atom and residue nomenclature • Compliance with PDB Exchange Dictionary • Data types, controlled vocabularies, parent-child relations • External tools such as WhatIF

36. PDBML/XML schema validation • Version control • Data type consistency • Data ranges • Controlled vocabularies • Referential integrity • XPath traversal of PDBML data hierarchy

37. Database loads • Diagnostics obtained from loading remediated data into existing database systems • Relational databases used by MSD-EBI and RCSB PDB • XML database used by PDBj

38. User-contributed diagnostics • Batch checking of remediated files by Phenix revealed consistency issues with alternate conformations - Ralf Grosse-Kunstleve • Batch checking for inconsistent linkages and missing residues by docking software - Tommy Carstensen • Nomenclature - Tom Goddard & Chimera Group • Sequence and assembly diagnostics - Roland Dunbrack • Relational data integrity diagnostics - Dan Bosler • Nomenclature and experimental details - Clemens Vonrhein • Many specific issues related to chemical assignments, disorder, and nomenclature

39. Looking toward the future Kim Henrick

40. Annotation project • Standardize annotation rules and policies among wwPDB sites • Document annotation rules and policies • Create venue to update annotation rules and policies as necessary

41. Annotation project How did we get there? • Review and discussion of each PDB field by email and VTC • Document written and reviewed by all staff • Final review by site directors • Software compliant to new annotation procedures implemented • Tested software and trained annotators • Published document on web (January 2007)

42. Annotation document • Specification of ALL fields in PDB file • Clarification of policies • Assignment of PDB IDs • Release of files and information • Changes to entries • Clarification of data representation • Chain ID for all atoms in the file • Multi-model representation for alternate conformation or disorder • Chimeras • Microheterogenity

43. PDB IDs and DOIs • Credit for a PDB entry in CVs • Used as a reference in publications • http://dx.doi.org/10.2210/pdb4hhb/pdb See also DOIs for Biological Databases Philip E. Bourne, CrossRef 7th Annual Meeting, 1 November 2006 Cambridge, MA

44. Outstanding issues • Microheterogeniety • Disorder • Large structures

45. wwPDB and software developers • ACA 24th July 2007 meeting in Salt Lake City • “Future Challenges for the PDB: What should the PDB be doing in 2015?” • Attended by software developers and wwPDB staff

46. July 24 meeting • Technical discussions • TLS • Multiple models • Large structure • demand for one file per structure • Microheterogeneity • Twinning • George Sheldrick, Paul Adams and Garib Murshudov produce a draft of the PDB format to describe twinning and to represent the data in HKLF • Procedural outcomes • Yearly developer meeting • Editorial board to assist in difficult annotation problems • Ongoing electronic forum

47. Toward a single processing tool • This weekend – wwPDB retreat with contributors from RCSB PDB Rutgers and UCSD, BMRB, PDBj, and EBI-EMBL • Task – come to agreement to pool resources to produce a single deposition tool and design of new processing pipeline