1. Worldwide Protein Data Bank www.wwpdb.org

2. Worldwide Protein Data Bank www.wwpdb.org Agenda  Welcome and Introductions  Overview of recent wwPDB progress  Introduction to the BMRB  Theoretical model policy  Issues for discussion and advice Break  wwPDB group interactions  wwPDB plans for 2007  Long term aims, funding, and stability  Executive session  Feedback to wwPDB  Set next meeting date (July 2007; Salt Lake City, UT?)

3. Worldwide Protein Data Bank www.wwpdb.org wwPDB Achievements August 2005-October 2006  Continued growth of archive  Website updates  Publications and presentations  Time stamped archive  wwPDB team building  Annotation document  Remediation  BMRB formally a member of wwPDB

4. Worldwide Protein Data Bank www.wwpdb.org Deposition issues

5. Worldwide Protein Data Bank www.wwpdb.org The never ending story

6. Worldwide Protein Data Bank www.wwpdb.org Deposition since establishment of 3 sites

7. Worldwide Protein Data Bank www.wwpdb.org PDB entry processing  1-1-2000 10,997 entries in PDB  Today 1-Oct-2006 39,323 entries in PDB Total size is 3.6 times when the 3 sites started  In 1999 2361 entries deposited  In 2005 6678 entries deposited We handle 2.8 as many entries per year with less staff - and all 3 sites produce high quality annotated PDB entries NO CURRENT BACKLOG UN-PROCESSED ENTRIES

8. Worldwide Protein Data Bank www.wwpdb.org Time-stamped copies of the archive  24 Gbytes of data for 2005, released January 3, 2006  Includes: –PDB format entries –mmCIF format entries –PDBML format entries –Experimental data –Dictionary, schema and format documentation

9. Worldwide Protein Data Bank www.wwpdb.org Outreach  wwPDB website  Publications and meetings

10. Worldwide Protein Data Bank www.wwpdb.org

11. Worldwide Protein Data Bank www.wwpdb.org Joint publications and presentations  Nucleic Acids Research 2007 Database Issue –Ensuring a single, uniform archive of PDB data  Methods in Molecular Biology 2007 –Data deposition and annotation at the wwPDB  Nature Structural & Molecular Biology, 2006 –Is one solution good enough? (response)  CODATA (October 23-25, 2006; Beijing, China) –The Worldwide Protein Data Bank  Encyclopedia of Genomics, Proteomics, and Bioinformatics, 2005 –The Protein Data Bank and the wwPDB

12. Worldwide Protein Data Bank www.wwpdb.org The wwPDB Team

13. Worldwide Protein Data Bank www.wwpdb.org wwPDB interactions this year  Exchange visits –MSD/RCSB (6) (thanks to WT) –PDBj/RCSB (1), –BMRB/RCSB-PDB (3)  Phone conference with site directors-twice a year  VTC’s among staff –BMRB/RCSB twice a month (ADIT-NMR) –MSD/RCSB-twice a week (annotation procedures, remediation)  Email among staff –MSD/RCSB~2 per day –PDBj/RCSB~2 per day

14. Worldwide Protein Data Bank www.wwpdb.org What is the PDB?  Content  Processes to ensure quality (annotation project)

15. Worldwide Protein Data Bank www.wwpdb.org Annotation project

16. Worldwide Protein Data Bank www.wwpdb.org Annotation project GOALS  Standardize annotation rules and policies among wwPDB sites  Document annotation rules and policies  Create venue to update annotation rules and policies as necessary

17. Worldwide Protein Data Bank www.wwpdb.org Annotation project How did we get there?  Review and discuss each PDB field by email and VTC  Write document and review by all staff  Final review by site directors  Implement software compliant to new annotation procedures  Test software and train annotators  Publish document on Web

18. Worldwide Protein Data Bank www.wwpdb.org Annotation project Resultant 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

19. Worldwide Protein Data Bank www.wwpdb.org Remediation

20. Worldwide Protein Data Bank www.wwpdb.org Remediation: scope 34,528 Entries Checked  Primary citations  Sequences & taxonomy  Ligand stereochemistry and nomenclature  Symmetry and coordinate transformations for virus entries  Diffraction source & beamline  Miscellaneous uniformity issues

21. Worldwide Protein Data Bank www.wwpdb.org Remediation: statistics  Citations : –All primary citations checked –8508 citations manually examined –7037 citations confirmed and updated  Sequence and taxonomy : –47917 sequences checked –20068 updated sequence data references –11087 taxonomic references updated  Virus entries –250 entries checked and revised  Diffraction source –10985 entries revised  Miscellaneous uniformity corrections –1041 entries revised

22. Worldwide Protein Data Bank www.wwpdb.org Remediation: statistics  Ligand stereochemistry and nomenclature –7568 ligand definitions checked –1758 new ligand definitions added –185 ligand definitions obsoleted –152,000 ligand instances checked –138,230 ligand instances OK –6815 ligand instances renamed

23. Worldwide Protein Data Bank www.wwpdb.org Remediation process  Corrections contributed and reviewed by wwPDB members  Corrections on the archival mmCIF data files tracked in a version tracking system, CVS  New PDB exchange, PDBML and PDB format data files being produced now  Each wwPDB group will validate and load the resulting files into their database systems  Invited public testing will begin January 2007  General availability will start April 2007

24. Worldwide Protein Data Bank www.wwpdb.org Remediation: Ligand dictionary rewrite  Model and idealized coordinates provided  Stereochemical configuration assignments  Aromatic atoms and bonds flagged  Definitions provided for “Chemistry Catalog” state with leaving atom candidates flagged  Nonstandard atom names revised (e.g. dinucleotides)  Duplicate ligand definitions marked as obsolete  Metal hydrate definitions obsoleted  Alternate atom name aded to store legacy atom names  SMILES and INCHI descriptors provided

25. Worldwide Protein Data Bank www.wwpdb.org Remediation: major entry level corrections  Citations: –PubMed identifiers provided where available –Unpublished citations checked and flagged  Sequence and taxonomy: –UniProt sequence database references –Taxonomies from NCBI Taxonomy database  Diffraction source –Synchrotron facility and beamlines names consistently specified in coordination with BioSync

26. Worldwide Protein Data Bank www.wwpdb.org Remediation: major ATOM record changes  Nomenclature changes –IUPAC H-atom names for standard amino acids and nucleotides –DNA and RNA differentiated (AD (DNA) & A (RNA)) –Modified nucleotides expressed as 3-letter codes (removed +’s) –PDB asterisks replaced by single quotes in atom names –Noncompliant ligands flagged in data files

27. Worldwide Protein Data Bank www.wwpdb.org Remediation: Major REMARK changes  Virus entries –Transformations from deposited frame to point symmetry and crystallographic frame provided –NCS and point symmetry transformations properly differentiated

28. Worldwide Protein Data Bank www.wwpdb.org EM standards  New dictionary for electron microscopy  MAP orientation conventions

29. BMRB John Markley Worldwide Protein Data Bank www.wwpdb.org

30. Introduction to the BMRB  BMRB is the worldwide archival site for biomolecular NMR data  NMR data related to structures are cross referenced to PDB entries  PDBj mirrors BMRB and supports external BMRB depositions  As RCSB members, BMRB and PDB have worked closely to capture and annotate NMR data associated with deposited coordinate sets  Recognizing that the biomolecular NMR community would be best served by having a “one stop” deposition system for NMR structures, BMRB has been pursuing this goal in collaboration with the RCSB-PDB  BMRB plans to institute the same policy with MSD EBL Worldwide Protein Data Bank www.wwpdb.org

31. Worldwide Protein Data Bank www.wwpdb.org wwPDB NMR experimental data flow RCSB-PDB (deposition) ADIT-NMR PDBj-BMRB (deposition/processing/export) ADIT-NMR Mirror site BMRB (deposition/processing/export) ADIT-NMR central archive MSD/EBI (deposition/export) CCPN Deposited data Raw NMR-STAR Deposited data Processed NMR- STAR CERM-BMRB (export) Mirror site Processed NMR-STAR Processed NMR-STAR Processed NMR- STAR

32.  “One-stop” BMRB-PDB ADIT-NMR deposition site for structures and NMR data developed in collaboration with PDB is operational, with BMRB assigning PDB accession codes  Restraints database for legacy structures is nearing completion as part of the wwPDB “clean-up”; new tools to automate this process were developed in collaboration with MSD EBI  NMR-STAR v3 dictionary has been extended and released  Graphical interface with Jmol displays integrates PDB coordinate data with associated NMR parameters  BMRB is working with SG groups to improve efficiency of capturing protein NMR data  BMRB participates in the “PDB-BMRB Task Group on NMR” Major developments related to BMRB’s role in the wwPDB Worldwide Protein Data Bank www.wwpdb.org

33. New “one-stop” deposition of NMR structures/ data Worldwide Protein Data Bank www.wwpdb.org

34.  BMRB and RCSB-PDB depositions are now generated from a joint interface  BMRB interface has been streamlined  RCSB-PDB interface for NMR has been extended with optional fields for conformer and constraint statistics  Files in PDB format, mmCIF, and NMR-STAR can be uploaded to pre-populate a deposition  Many fields (i.e., experiment name, software name, software author, etc.) have pull-down lists to choose from for convenience and to improve uniformity  Fields common to multiple forms are linked to eliminate the need to retype information (i.e., uploaded data file names, author names, molecule names and others)  Help and examples have been improved Deposition interface features Worldwide Protein Data Bank www.wwpdb.org

35. Worldwide Protein Data Bank www.wwpdb.org Restraints grid is keyed to NMR structural entries

36. Worldwide Protein Data Bank www.wwpdb.org Coordinated displays of NMR data and structures

37. Worldwide Protein Data Bank www.wwpdb.org Theoretical Models Policy Haruki Nakamura

38. Worldwide Protein Data Bank www.wwpdb.org Models  Define line between “pure” models and models based on data  Large experimental spectrum e.g. X-ray, NMR, EM, SAX, FRET models  Homology models especially as derived from structural genomics  Need a way to archive models that is totally compatible with PDB

39. Worldwide Protein Data Bank www.wwpdb.org Defining a policy for models  Attended by modelers, structural genomicists, electron microscopists  Policies and suggested implementations developed  Outcome published in Structure –“Outcome of a Workshop on Archiving Structural Models of Biological Macromolecules”, Helen M. Berman, Stephen K. Burley, Wah Chiu, Andrej Sali, Alexei Adzhubei, Philip E. Bourne, Stephen H. Bryant, Roland L. Dunbrack, Jr., Krzysztof Fidelis, Joachim Frank, Adam Godzik, Kim Henrick, Andrzej Joachimiak, Bernard Heymann, David Jones, John L. Markley, John Moult, Gaetano T. Montelione, Christine Orengo, Michael G. Rossmann, Burkhard Rost, Helen Saibil, Torsten Schwede, Daron M. Standley, John D. Westbrook, Structure, 2006 14/8:1211-1217. Workshop at Rutgers (November 19-20, 2005)

40. Worldwide Protein Data Bank www.wwpdb.org Models Recommendations  PDB depositions will be restricted to atomic coordinates that are substantially determined by experimental measurements on specimens containing biological macromolecules.  A central, publicly available archive or portal should be established for models that are the explicit subject of peer review.  Methods for assessing model quality are essential for the integrity and long-term success of any publicly available model portal, either from a central repository or a set of linked resources. There was no consensus as to which single method or group of methods should be applied.

41. Theoretical Model DB 1 Theoretical Model DB 2 Proposed Portal for Multiple Databases for Protein Structures Berman, H. et al. (2006) Structure, 14, 1211-1217. Theoretical Model DBs

42. Worldwide Protein Data Bank www.wwpdb.org Characteristics of portal  Data Standards for Models  Access Models for a Central Portal of Models –The minimum contents for this portal require a unique identifier for each model registered with the system, each model's polypeptide chain sequence, and quality assessment information. –Additional information should be available, including: keywords, structural motifs, standard test sets of data, bound ligands, domains, flexibility, surface electrostatic properties, coding & noncoding SNPs, alternative splicing, oligomeric state, macromolecular interactions, literature references, subcellular localization, pathways, transcript profiling, & drugability. –Access to these data should be free and constantly available to a diverse worldwide user community of both model producers and users. Several levels of access are required for the different levels of users of the portal.

43. Worldwide Protein Data Bank www.wwpdb.org Implementation of models policy  August 15, 2006: Policy announced with 60 day period of review  August 15-October 15, 2006: Transition Plan –All existing un-processed theoretical model entries as well as entries deposited during this time were not validated or processed. Entries will be released as-is without author review or corrections. –Authors had the choice of correcting their entries by withdrawing the original entry and then re-submitting the corrected version before October 15, 2006.  October 15, 2006: Theoretical model depositions no longer accepted

44. Worldwide Protein Data Bank www.wwpdb.org Discussion Issues Kim Henrick

45. Worldwide Protein Data Bank www.wwpdb.org SAX - New EXP TYPE  Hamburg to provide templates for consideration

46. Worldwide Protein Data Bank www.wwpdb.org 4-letter code?  Use of PDB 4-letter code can be extended by allowing alpha-numeric in 1 st character to 35 x 36 x 36 x 36 = 1,632,960 combinations

47. Worldwide Protein Data Bank www.wwpdb.org Patent Office The structures in the patent office may not represent a major loss of structures – current investigations indicate most patent structures are in the PDB. A much larger set of structures are in the Pharma on ligand bound structures.

48. Worldwide Protein Data Bank www.wwpdb.org wwPDB SAC input request

49. Worldwide Protein Data Bank www.wwpdb.org What is a PDB Entry? Rules for the smallest structure that can be submitted –Carbohydrate chains? –How long is a peptide? (24) –Non-gene product macromolecular biological ligands (e.g. antibiotics)? Particular request from NMR depositors

50. Worldwide Protein Data Bank www.wwpdb.org Issues Annotation: EXP details Experimental Details  Twinning – twin factor in REMARK 3 requested and original un-twinned structure factors  TLS and conventional atomic B factor  Author derived Validation software and procedures/results – no longer accepted as in REMARK 42 – now a REMARK to carry software used and function

51. Worldwide Protein Data Bank www.wwpdb.org Policy: pre-Release Details  Entries on HOLD or HPUB – currently details usually made public – AUTHOR, TITLE, STATUS  Authors request all details suppressed – however Journals need to check validity of IDCODE...Yes/No?

52. Worldwide Protein Data Bank www.wwpdb.org Deposition policy  HPUB/HOLD limit of one year Current problem: After one year no response. Do we release?... fixed rules? No problems, release it Problems, withdraw it

53. Worldwide Protein Data Bank www.wwpdb.org Major changes after remediation dictionary changes  Could have major affects on software  New dictionary will be announced to many software developers in early November, 2006

54. Worldwide Protein Data Bank www.wwpdb.org Major changes after remediation nucleic acids –DNA and RNA differentiated (AD (DNA) & A (RNA)) residue names now A = rna, AD = dna –Modified nucleotides expressed as 3-letter codes (removed +’s) e.g. no longer treat as +C etc C31 as 2'-O-3-AMINOPROPYL CYTIDINE-5'- MONOPHOSPHATE –PDB asterisks replaced by single quotes in atom names O2* is back to O2’ as in refinement dictionaries

55. Worldwide Protein Data Bank www.wwpdb.org IUPAC H-atom names for standard amino acids and nucleotides as in BMRB file http://www.bmrb.wisc.edu/ref_info/atom_nom.tbl as recommended by the NMR Task Force Example New PDB New PDB New PDB H H HG12 pro-R 1HG1 HD11 1HD1 HA HA HG13 pro-S 2HG1 HD12 2HD1 Major changes after remediation H-atom names

56. Worldwide Protein Data Bank www.wwpdb.org Major changes after remediation other atom names  “strange” atom names as in co-factors like FAD i.e. AC1*, AN9, AC8 to be replaced by C1'A, N9A, C8A  In HEM atom names ‘N A’ to 'NA'

57. Worldwide Protein Data Bank www.wwpdb.org Other issues

58. Worldwide Protein Data Bank www.wwpdb.org Issues Annotation: Disorder/MODEL  Use of MODEL record with disorder with Alternate conformations of large portions of structures e.g. statistical disorder....in progress

59. Worldwide Protein Data Bank www.wwpdb.org Issues Annotation: ATOM/SEQRES Mismatch Fitting species specific ATOM records to a related X-ray or EM data set of a different species, as for example, a large complex, ATPase... needs new tokens in progress

60. Worldwide Protein Data Bank www.wwpdb.org Very large structures in PDB  A proposed solution

61. Worldwide Protein Data Bank www.wwpdb.org Representing large complexes in the PDB PART and ENDPRT These records will act much like the existing MODEL/ENDMDL records providing a sectioning mechanism with the PDB file. PART sections will include records which describe the different constituent parts of a large molecular system.

62. Worldwide Protein Data Bank www.wwpdb.org Representing large complexes in the PDB A PART/ENDPRT section will include all of the PDB records types which reference specific structural elements of the molecule. PDB records that do not define or reference specific elements of molecular structure will be at the beginning of the multipart PDB file

63. Worldwide Protein Data Bank www.wwpdb.org Coffee

64. Worldwide Protein Data Bank www.wwpdb.org wwPDB in 2007  Same again.. but more of it (deposition and processing) IN ADDITION  Rollout new files  Implement new annotation procedures  Discuss feasibility of a single deposition/processing system  Further team exchanges  Gather Pharma structures

65. Worldwide Protein Data Bank www.wwpdb.org Long term goals, funding and stability

66. Worldwide Protein Data Bank www.wwpdb.org We would really like to be the world wide PDB with regular stable funding

67. Worldwide Protein Data Bank www.wwpdb.org Acknowledgements E-MSD is supported by grants from the Wellcome Trust, the EU (TEMBLOR, NMRQUAL and IIMS), CCP4, the BBSRC, the MRC and EMBL. The BMRB is supported by NIH grant LM05799 from the National Library of Medicine. PDBj is supported by grant-in-aid from the Institute for Bioinformatics Research and Development, Japan Science and Technology Agency (BIRD-JST), and the Ministry of Education, Culture, Sports, Science and Technology (MEXT). The RCSB PDB is supported by grants from the National Science Foundation, National Institute of General Medical Sciences, the Office of Science-Department of Energy, the National Library of Medicine, the National Cancer Institute, the National Center for Research Resources, the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Neurological Disorders and Stroke, and the National Institute of Diabetes & Digestive & Kidney Diseases.