November 6 2009 www wwpdb org November 6

November 6, 2009 www. wwpdb. org

November 6, 2009 Agenda Summary Overview Haruki Nakamura Common Deposition and Annotation Tool Martha Quesada Method- and Moleculespecific Activities John Markley Gerard Kleywegt Policy and New Ventures Helen Berman PDB Journal Matt Day

Worldwide Protein Data Bank November 6, 2009 www. wwpdb. org Summary Overview Haruki Nakamura

November 6, 2009 ww. PDBAC 2008 Recommendations § § § § § Establish validation procedures for X-ray and NMR – X-ray Task Force draft report; NMR Task Force established Establish recommendations for additional data deposition and release requirements – Policy document updated Work with SAXS/SANS community – First report completed Definition of purview of the PDB – For approval at this meeting Establish feasibility of chemical shift depositions – Implementation plan Independent funding for ww. PDB – ww. PDB Foundation established Develop ww. PDBAC membership plan – Done Establish EM Task Force – First EMDB AC Meeting held March 2009 Broaden ww. PDBAC to include China and India – Associate Members: Zihe Rao (China) and Manju Bansal (India)

November 6, 2009 ww. PDB October 2008 - September 2009 § § § § § New Leadership PDBe-Gerard Kleywegt Funding stable at 4 sites Continued growth of archive Increased use of data PDB Archive Version 3. 15 released: archival snapshots Further coordination of FTP and web updates Common Tool Project underway Establishment of ww. PDB Foundation Continued outreach

November 6, 2009 Funding § RCSB PDB competitive renewal funded by NSF – January 2009 - December 2013 § PDBe competitive grant from Wellcome Trust – December 2009 - November 2014 – Additional new permanent EMBL posts-from 2013: stable core of at least 15 permanent posts (from 6 in 2008!) § PDBj competitive renewal funded by JST (Japan Science & Technology Agency) – April 2006 - March 2011: Current program – April 2011 - March 2014: A new funding system for life-science databases is planned § BMRB competitive renewal funded from the National Library of Medicine – September 2009 – August 2014 (parent grant) – September 2009 – August 2011 (administrative supplement – US recovery act funding) – September 2009 – August 2011 (competitive renewal – US recovery act funding)

November 6, 2009 PDB Depositions By deposition and processing site *(projected) (*8322) By experimental type

November 6, 2009 Increase of PDB data depositions from Asia and Oceania regions India New Zealand Australia Taiwan Hong Kong China

November 6, 2009 PDB Downloads * 1 st month after version 3. 0/3. 1 files released * 1 st month after version 3. 15 files released

November 6, 2009 PDB FTP Traffic (July 2008 - June 2009) RCSB PDB 200 million data downloads PDBe 37 million PDBj 14 million data downloads

November 6, 2009 Remediation Rollout § Complete PDB File Format Contents Guide Version 3. 20 released (Sep 2008) § PDB format version 3. 15 files released (March 2009) – New records/remarks: describe models, ligands and zero occupancy atoms/residues – Enhancements: assemblies, SITE records, chain IDs, database references (including taxonomy id, Pub. Med, DOI IDs) added for all files – Various corrections (including sequence, beamline, wavelength, atom connectivities, atom nomenclature, mm. CIF consistency) – Missing remarks restored

November 6, 2009 Common Tool for Deposition and Annotation Manage increased data load without an increase in resources § Create global deposition and annotation tools § Proof of concept delivered July 2009 § First test system due June 2010

November 6, 2009 ww. PDB Foundation § Will enable funding for ww. PDBAC meetings and outreach activities § Bylaws created § Paperwork filed

November 6, 2009 Outreach § Joint publications § Meeting posters, exhibit booths, and presentations – e. Chem. Info, EMBO Practical Course: Macromolecular Crystallography, Biophysical Society, Experimental Biology, Biocuration Meeting, ISMB/ECCB, Protein Society, ACA, ACS, As. CA § Website § Helpdesk Se Won Suh At As. Ca’ 09 Beijing Mitchell Guss

November 6, 2009 Formalized Internal Communications § Phone conferences among site directors § Regular exchange visits § Weekly VTC’s among staff – Common Tool – EM – NMR – Data annotation § Electronic reporting (validation, structure assignments, FTP updates, etc. ) ww. PDB Retreat 2009

Worldwide Protein Data Bank November 6, 2009 www. wwpdb. org Common Deposition and Annotation (D&A) Tool Martha Quesada

November 6, 2009 2007 ww. PDB Retreat COST What strategic objectives should we start to address now to meet our goals in the next 5 – 10 years? IMPACT

November 6, 2009 Drivers and Opportunities ww. PDB Common D & A Tool Project § § § New deposition types: multiple methods and new data New validation procedures Need to support higher throughput Limited resources for new development and maintenance Process inefficiencies – Redundant tools in use: Auto. Dep and ADIT, data harmonization required § Good collaborations among sites – Possibility of sharing of workload – Precedent for common tools for NMR and EM

November 6, 2009 Inflection Point Change the game Usage, Impact New capabilities Ready for today Business as usual Time Decision to come together as the ww. PDB in developing the tools that will support the shared functions of the ww. PDB for the next 10 years

November 6, 2009 ww. PDB Common D&A Tool Project The goal is to implement a set of common deposition and annotation processes and tools that will enable the ww. PDB to deliver a resource of increasingly high quality and dependability over the next 10 years. § The tools will address: the increase in complexity and experimental variety of submissions and the increase in deposition throughput § The processes and tools will maximize the efficiency and effectiveness of data handling and support for the scientific community

November 6, 2009 Project Scope § Common deposition interface and processing – – Coordinates (x, y, z) regardless of experiment origin (X-ray, NMR, EM) NMR restraints, chemical shifts X-ray structure factors 3 D-EM maps § Data processing: Validation Tools – – – Fit of model to data Coordinates for polymers and ligands NMR Restraints Structure factor validation EM map validation Partly developed by External Task Forces To be integrated over time

November 6, 2009 Assumptions & Constraints § Functional requirements – Deposition tool must handle all current, agreed upon data entry and report formats from the user community – All data elements covered within the PDB annotation manual must be included § Technical requirement – Design will enable flexibility for growth and evolution – Technical level reasonable standard, not bleeding edge or declining – Design must enable integration with community data capture

November 6, 2009 For example § Deposition will capture all currently deposited experimental data for each method § The tool will support all data formats and validation requirements for all deposition types § The system will allow for workload balancing during deposition

November 6, 2009 Common D&A Project Characteristics Large and complex – Break into smaller bits Distributed developers – Establish development controls and communication Some requirements well understood – Policies in place Some requirements evolving Iteration 1 1. 2. 3. Potentially novel designs require early experimentation 5. 4. Increment delivered Review lessons learned 6. Iteration 2 1. 2. 3. 5. 4. 6. Iteration n 1. 2. 3. 5. 4. 6. Etcetera…

November 6, 2009 Modern Requirements Analysis § Process (workflow) driven: As is vs. To be – – What exactly do we actually do? Analyze current processes What works and where are the opportunities? What would be the ideal process? § Alignment of requirements to workflow – Functional requirements § calculations, decision trees, reports, communication – Data flow requirements – Technical (strategic and tactical) requirements

November 6, 2009 Project Phases, Structure and Roles Initiation Concept Reqmt Design Develop & Test Delivery § Steering Committee – Governance – Milestone reviews and guidance § Concept Team – Initial requirements and design § Core Team (Functional leaders) – Plan and manage the project § Project Teams – Design, develop and test component solutions – Deliver the solution

November 6, 2009 Communication and Coordination § Among all of the project stakeholders – Inward facing – Outward facing § Between distributed functional and development groups

November 6, 2009 Initiation Concept Steering Committee (ww. PDB Directors) October 2007 § Set project Project Goal, Scope, Assumptions and Constraints, initial timelines § Approves project at each milestone Concept Team November 2007 § Objectives, strategies and metrics § Stakeholder analysis & risk assessment § New system requirements § Concept process maps Approved May 08

November 6, 2009 Objectives & Strategies § Improve data quality beginning at data capture – Provide for interactive feedback and value to the depositors during the deposition process – Employ community-driven validation methods § Improve efficiency – Standardization, automation and more flexible data sharing § Improve existing tools – Use “best of breed” existing tools where possible – Free resources to redevelop/develop new common tools § Enable system maintenance and evolution – system modularity

November 6, 2009 Initiation of Design and Planning Reqmt Design The Core Team, representing the functional groups and sites, leads the project through design and implementation in conversation with the Steering Committee Develop & Test RCSB PDB: John Westbrook, Jasmine Young; PDBe: Tom Oldfield, Sameer Velankar, Jawahar Swaminathan; BMRB: Steve Mading, Eldon Urlich; PDBj: Takanori Matssura

November 6, 2009 Project Team: Distributed Reqmt Design Develop & Test Delivery § Quarterly face-toface meetings § Weekly VTC team working meetings § On-going teleconferences and email § Shared web-based document and code management tools Subject and technical experts from all sites

November 6, 2009 Key Design Elements Modular construction through an API • Reuse of “best of breed” existing tools; redevelop tools as time and need dictate. • Enable system maintenance and evolution Improved workflow efficiency for faster processing • Workflow automation - workflow engine and manager Improved collaboration • More flexible data sharing Proposed technical design and deliverables reviewed and approved by the Steering Committee

November 6, 2009 July 2009 Technical Design Proof Of Concept Potentially novel designs require early experimentation § Application Programming Interface: API – “wrapped” application functionality § Faster processing through improved efficiency – workflow automation implementation § Improved collaboration – Snapmirror tested Workflow Engine Python Core API Layer C/C++ Apps Fortran Apps RDBMS Other Services

November 6, 2009 January 2010 - Production Deliverable § Implementation of an annotation module Expansion of workflow proof of concept Implementation of the API using existing functionality and the “Master Format” Introduction of “Go Back” functionality Improved user interface Integrated with existing workflows. With GO BACK functionality

November 6, 2009 Project Progress § July 2008: Initiate Design and Development Planning (Core Team) § Nov 2008: Define Data Model Requirements (Project Team Meeting), Flesh out Design elements § March 2009: Finalized design elements and initiate development of “proof of concept” § July 2009: Deliver design “proof of concept” § January 2010: First production deliverable Initiation Concept 4 Q 2007 Requirements Design 2008 Development Test 2009 Delivery 2010 2011

November 6, 2009 ww. PDB Common D&A Tool Project Timeline Going Forward Initiation Concept 4 Q 2007 Requirements Design 2008 Concept § Define deliverables § Initial design § Process definition § Data model definition § Development Test 2009 Delivery 2010 Requirements elaboration §production § Data flow documentation deliverables § Technical Design § Data Sharing & Replication § API, Master Format § Automated Workflow § Technical Proof of Concept § Development of initial production deliverable • Communication design § 2011 D&A system delivery §

November 6, 2009 Ultimate Project Deliverables § For Depositors – Interactive and informative deposition interface – Value added validation input and annotation during deposition – Faster processing § For Annotators – Improve efficiency, freeing time for more advanced annotation § Improved quality early in the process § Automation of appropriate processing steps § Best of breed tools § Expanded functionality – Enable system maintenance and evolution through system modularity § For Data Users – Higher Quality Archive

Worldwide Protein Data Bank November 6, 2009 www. wwpdb. org Method and Molecule-specific Activities John Markley Gerard Kleywegt

November 6, 2009 NMR

November 6, 2009 NMR Update § Remediated NMR restraints project is near § NMR Validation Task Force established – First meeting held Sept 21, 2009, in Paris, France § Implementation plan for Chemical Shifts requirement in progress § Status of SMSDep

November 6, 2009 NMR Validation Task Force: Charge § Advise on validation of new NMR data depositions § Provide a report for the ww. PDB AC § Provide recommendations for structure validation criteria and tools – Tools and procedures recommended should be freely available and simple to install and maintain so users can easily use in own laboratories – Tools should not be used as a basis to “reject” structures, but to flag potential problems for the depositor/user to be aware of – Recommendations should be assembled into a “white paper” for publication – Recommendations should be targeted to software developers, depositors, journal editors, and PDB users

November 6, 2009 NMR Validation Task Force Committee Members Gaetano Montelione (Co-Chair, Rutgers) Michael Nilges (Co-Chair, Institut Pasteur) Ad Bax (NIH)* Peter Guentert (University Frankfurt) Torsten Herrmann (CNRS/ENS Lyon) Jane Richardson (Duke University) Charles Schwieters (NIH) Geerten Vuister (Radboud University)* David Wishart (University of Alberta) * Notes on the Paris meeting Ad Bax and Eldon Ulrich were unable to attend the meeting Jurgen Doreleijers attended as a substitute for Geerten Vuister Meeting Observers Naohiro Kobayashi (PDBj-BMRB) John Markley (NMR VTF Organizer) Randy Read (Chair, X-ray VTF) Eldon Ulrich (BMRB)* Wim Vranken (PDBe) John Westbrook (RCSB PDB)

November 6, 2009 NMR VTF: Outcome of first meeting September 21, 2009; Paris, France § General consensus on the value of expanded NMR validation for the scientific community. § Consensus on coordination with X-ray VTF on common validation issues. § Requirements and available tools for validation were assessed during the meeting. § Areas targeted for further research: format consistency for restraints, treatment of internal dynamics and ensemble averaging. § Website and mail archive created to support task force communication

November 6, 2009 Chemical Shifts: Progress in implementation § BMRB has been the primary deposition and processing site for NMR chemical shift (CS) data § Mandatory chemical shift and reference data items have been defined, and a prototype mandatory CS system is in place § ww. PDB to perform minimal processing: – check format and sanity check at deposition – substitute explicit atoms for pseudo-atoms – maintain nomenclature correspondence during annotation § Data files are to be transferred to BMRB for further annotation § PDB will release chemical shift files in NMR-STAR format along with coordinate data files § Download statistics for chemical shift data files will be be maintained for BMRB (needed for grant reporting)

November 6, 2009 SMSDep § Deposition system is in place and accepting structures and associated NMR chemical shifts § Current policy is to accept data only for small peptides or nucleic acids (processing and annotation is carried out at PDBj-BMRB) § We need to monitor the level of activity to determine whether this site should be maintained

November 6, 2009 X-ray

November 6, 2009 ww. PDB X-ray Validation Task Force § Initial meeting – April 14 -16, 2008 EBI, Hinxton, UK – R. Read (Chair), P. Adams, A. Brunger, P. Emsley, R. Joosten, G. Kleywegt, E. Krissinel, T. Luetteke, Z. Otwinowski, T. Perrakis, J. Richardson, W. Sheffler, J. Smith, I. Tickle, G. Vriend § Goal – Gather recommendations and consensus on additional validation for PDB entries, and identify software applications for these validation tasks – Provide code/algorithms for the validation-software pipeline § Preliminary Outcome – Candidate global and local validation measures were identified – These measures were reviewed in terms of the requirements of depositors, reviewers, and users

November 6, 2009 X-ray Validation Task Force: Next Steps § May 2008 - September 2009: discussions (e-mail, Gordon Conference) and report writing § October 2009: Meeting to complete report during Cold Spring Harbor Laboratory Crystallography Course § November 2009: Report presented at ww. PDBAC § ww. PDB partners are pooling manpower to implement Task Force recommendations – One dedicated programmer to implement the validation-software pipeline (Swanand Gore) § Validation tools and procedures will also be incorporated in the new ww. PDB Common Deposition and Annotation system

November 6, 2009 ww. PDB X-ray Validation Task Force § Apply new knowledge of structure – proteins, nucleic acids, carbohydrates, ligands § New opportunities from mandatory data – fit to data, quality of data, pathologies § Exploit new technologies – machine-readable annotation § Serve the different communities – users, depositors, editors/referees

November 6, 2009 Ramachandran revisited

November 6, 2009 Clashes and holes

November 6, 2009 One intuitive summary of quality

November 6, 2009 Members of X-ray VTF Paul Adams Axel Brunger Paul Emsley Roobie Joosten Gerard Kleywegt* Eugene Krissinel Thomas Lütteke Zbyszek Otwinowski Tassos Perrakis Jane Richardson Will Sheffler Janet Smith Ian Tickle Gert Vriend Randy Read

November 6, 2009 SAXS/SANS

November 6, 2009 SAXS/SANS § Increase of SAS publications for structural biology 200 180 160 140 120 100 – Higher intensity sources – Advances in data analysis and modeling tools § Increase in number of deposition requests since 2005 80 60 40 20 0 1985 1990 1995 2000 2005 2010 Number of hits from simple search of publications by using protein structure and small angle scattering

November 6, 2009 SAXS/SANS: Current Status § Two types of models – Atomic model with a directed sequence – Dummy residue model § 41 structures have been deposited since 1998 Model 1 – 7 Model 1 – 2 Model 2 (withdrawn) – 32 are between Model 1 and 2 (chain of C ) Model 2

November 6, 2009 ww. PDB proposed requirements for a SAXS/SANS PDB entry § Model is derived and fully defined by the experimental data § Model is a folded chain of residues with directionality § COMPND, SOURCE, SEQRES and external sequence reference (DBREF) are included § x, y, z coordinates per atom. Cα or P model allowed § Has acceptable geometry (bond-length, bond-angle, torsion-angle, nonbonded contacts, etc. ) § Experimental and refinement details recorded in appropriate REMARK records § Parameters directly derived from the scattering profile should be supplied and appropriately recorded (radius of gyration, Dmax in distance distribution function, mass, etc. ) § Reduced 1 D experimental profile § Family of models should be superimposed

November 6, 2009 SAXS/SANS: Next Steps § Create a SAXS/SANS Task Force to advise the ww. PDB – Which if any SAXS/SANS models should be in PDB? – Template for PDB file – Validation standards

November 6, 2009 Electron Microscopy

November 6, 2009 Electron Microscopy § Collaborative project between RCSB PDB, PDBe, and Baylor-NCMI is funded by NIH, BBSRC, and EMBL § Unified tool for collecting model coordinates and map files in a one-stop shop § Merge deposition and annotation with PDB as part of Common Tool by 2011

November 6, 2009 EM Coordinate and Map Depositions

November 6, 2009 EMDatabank. org § Joint map + coordinate deposition service § Emdatabank. org: news, EM software list, information about dictionaries, conventions, FAQ page, community links § EMSEARCH: search by ID, author, sample type, keyword, deposition date § EMViewer: simple map viewer

November 6, 2009 EMDB Annotation § 1 EBI annotator in 2002 § 1 RCSB PDB annotator added in 2008 § Joint deposition of map and model enables joint validation § Annotation document has been written § Remediation underway to improve uniformity of maps and header XML files § Letters sent to journals about deposition requirements

November 6, 2009 EM Navigator Service provided by PDBj: Search for EM data through EMDB with the corresponding PDB data n Views of EM 3 D structures with or without the relating atomic structures in PDB as movies and by molecular viewers n Will test the newly remediated EM map files so as to ensure the quality of these files

November 6, 2009 Next steps § Community input on modeling criteria for EM maps-First meeting January 2010 § Set up EM Task Force to set deposition and validation standards for deposition § Set requirements for EM for the Common Tool project § Target date for incorporation of EM maps into the PDB-2011

November 6, 2009 Complex Chemistry of Peptide. Like Molecules in the PDB: Antibiotics and Inhibitors

November 6, 2009 Challenges § Inclusion of non-standard amino acid, nucleotides, or other chemical groups in sequence § Non-linear (cyclic or branched) sequences § Microheterogeneity (some cases) § Non-uniform annotation of the same molecule in different PDB entries § Lack of annotation regarding the source and function of these molecules

November 6, 2009 Solutions § Analyze and classify – Groups antibiotics and inhibitors into polymeric molecules or single components § § Chemical Component Dictionary updates Remediate files Establish rules for future processing Create Peptide Reference Dictionary

November 6, 2009 Peptide-Like Molecules: Inhibitors § Combined (single component) (406) FFRCK; PPACK II Subcomp: DPN PHE ARG 0 QE § Retained as polymer (350) Leupeptin Ace-Leu-Argal 1 2 3 4 § Split to polymer (23) Pepstatin IVA VAL STA ALA STA 1 2 3 4 5 6

November 6, 2009 Peptide-Like molecules: Antibiotics Split for clear and correct representation (180) Actinomycin D (non-ribosomal product) THR DVA PRO SAR MVA PXZ THR DVA PRO SAR MVA 1 2 3 4 5 6 7 8 9 10 11 Thiostrepton (gene product) I 1 A 2 S 3 A 4 S 5 C 6 T 7 T 8 C 9 I C T C S S 10 11 12 13 14 15 16 17

November 6, 2009 Peptide Reference Dictionary (PRD) § Initial research completed (summer interns) § Checking and corrections (in progress) § Information to be incorporated in remediated files § Dictionary to be made available to all

November 6, 2009 Status of Peptide-Like Molecules § Inhibitor remediations (RCSB PDB) § Antibiotic remediations (PDBe) § Expected release: Spring 2010

Worldwide Protein Data Bank November 6, 2009 www. wwpdb. org Policy Issues and New Ventures Helen Berman

November 6, 2009 Molecules Accepted by ww. PDB Current Requirement: § Polypeptide structures with 24 or more residues § Polynucleotide structures with 4 or more residues § Polysaccharide structures with 4 or more residues

November 6, 2009 Molecules Accepted by ww. PDB Proposed Requirement § Polypeptide structures – – Gene products Naturally-occurring non-ribosomally synthesized peptides Peptidic repeat units of large fibrous polymers Synthetic peptides of at least 24 residues unless there is a clear case that it is of biological relevance § Polynucleotide structures – With 4 or more residues § Polysaccharide structures – With 4 or more residues

November 6, 2009 PDB Format Problems § Large structures not accommodated in current format – > 62 chains – 99999 atoms § § Level of experimental detail Multiple models Non-homogeneous models Non-linear sequences (e. g. , carbohydrates)

November 6, 2009 Proposal § Create a modified PDB format for ATOM and others records such that is possible to – calculate electron-density maps – validate of the model and its fit to the experimental data – continue or re-do the refinement § Meta data would be represented in PDBx § Small group of key community members would be consulted § New format in place by Q 4 2010

November 6, 2009 Status Code Clarification Author Approval of Annotation Report? No Author Response & No issues No Author Response & Entry has Issues & Paper is published No Author Response & Entry has Issues & No paper is published Release after 3 weeks Release with CAVEAT record upon electronic publication of corresponding paper Withdrawn 12 months after deposition REL Release immediately HPUB Release upon electronic publication Release with CAVEAT record upon electronic publication of corresponding paper HOLD At most a year after deposition; entry is released upon electronic publication based upon journal policy At most a year after deposition; entry may be released upon electronic publication based upon journal policy Release with CAVEAT record upon electronic publication of corresponding paper

November 6, 2009 Obsolete Entries § Appears in entries that have been removed from main distribution into ftp: //ftp. wwpdb. org/pub/pdb/data/structures/obsolete/ § It is PDB policy that only the principal investigator and/or the primary author who submitted an entry has the authority to obsolete it § OBSLTE indicates which, if any, new entries have replaced the entry that was obsoleted (SPRSDE) § Explanation for obsolete entries without replacement entry should be included in files

November 6, 2009 Fabricated Structures Problem: A PDB entry is found to be fabricated Proposed Action: If the author does not agree to OBSLTE the entry, the employer of the author may request that PDB entry be made OBSLTE. This request must be appropriately documented. The citation for the obsolete entry must be a published explanation of the circumstances that led to retraction of the paper(s) and associated PDB entry or entries.

November 6, 2009 Worldwide Protein Data Bank Foundation, Inc. § Organized to benefit the public and to support and ensure the functioning of the ww. PDB AC § Conducts the annual review meeting to ensure the continued effectiveness of the collaboration § Conducts seminars and workshops with the purpose of educating the public and promoting the goals and activities of the ww. PDB in curation, archiving, and disseminating the common data archive of biological macromolecules § Fundraising initiatives include journal and donations

November 6, 2009 Worldwide Protein Data Bank Foundation, Inc. § Bylaws filed with the state of New Jersey § Board of Trustees – 4 members, one elected by each ww. PDB site § Officers – Elected by the Board of Trustees – President, Secretary, Treasurer

November 6, 2009 Industrial Interactions § Increased interactions/collaborations with software companies: Open. Eye, CCG, Schrodinger leading to improved data files § US-CSAR: Community Structure Activity Resource are collecting model and binding data from pharma. Refined structures will be sent to PDB § Europe-Innovative Medicines Initiative's Open Pharma Space may provide a source of industrial models