www.wwpdb.org

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www.wwpdb.org
September 7, 2007
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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

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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

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Depositions since wwPDB establishment
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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

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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

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Outreach

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

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(No Transcript)
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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, 14354 (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

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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
• VTCs 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

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New initiatives

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

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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

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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

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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

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Remediation
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Key drivers

• Chemistry and nomenclature
• Sequence and taxonomy
• Citations
• Viruses

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IUPAC, NMR, and the PDB Atom nomenclature and
NMR restraints

• John L. Markley

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History of the NMR-led requested remediation of
hydrogen atom nomenclature

• When BMRB was established in the late 1980s, 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

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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

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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

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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

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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

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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

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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

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Most X-ray structures are supported by structure
factors
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Less than half of NMR structures are supported by
restraint data
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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
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Remediation rollout

• Helen M. Berman

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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

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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

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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

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Checking the remediated files

• Haruki Nakamura

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Different checks

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

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References to external databases

• Sequence and taxonomy (UniProt)
• Primary Citations (PubMed)

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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

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PDBML/XML schema validation

• Version control
• Data type consistency
• Data ranges
• Controlled vocabularies
• Referential integrity
• XPath traversal of PDBML data hierarchy

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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

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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

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Looking toward the future

• Kim Henrick

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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

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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)

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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

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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
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Outstanding issues

• Microheterogeniety
• Disorder
• Large structures

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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

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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

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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