PDB-Dev and Integrative Modeling
PDB-Dev is a prototype deposition and archiving system for structural models obtained using integrative or hybrid modeling. Structures of complex macromolecular assemblies are increasingly determined using integrative modeling, where a combination of complementary experimental and computational techniques is employed to model the structures. In addition to traditional structure determination methods such as X-ray crystallography (X-ray), NMR spectroscopy (NMR), and Electron Microscopy (3DEM), experimental techniques such as small angle scattering (SAS), atomic force microscopy (AFM), chemical cross-linking (CX), co-purification, Förster resonance energy transfer (FRET), electron paramagnetic resonance (EPR), mass spectrometry (MS), Hydrogen/Deuterium exchange (HDX), and various proteomics and bioinformatics approaches contribute to integrative modeling. Spatial restraints derived from the different kinds of experimental and computational methods are combined to derive the structure of the macromolecular assembly. Integrative modeling has been applied to determine the structures of complexes such as the nuclear pore complex and its sub-complexes, 16S rRNA complexed with methyltransferase A, human mitochondrial iron sulfur cluster core complex, the BBSome, ghrelin bound to its G protein-coupled receptor, complex of RNF168-RING domain and the nucleosome.
We have developed a data dictionary for archiving structural models of macromolecular assemblies derived through integrative/hybrid methods. The IHMCIF dictionary defines the data specifications required for archiving the integrative structural models, the associated spatial restraints and modeling protocols. This dictionary is a logical, modular extension of the PDBx/mmCIF dictionary currently used by the wwPDB for archiving atomic structures of macromolecules. The new dictionary extends the definitions in the PDBx/mmCIF dictionary in five significant aspects that address the requirements for archiving integrative models:
- Allows for a flexible model representation with descriptions for atomic and coarse-grained objects
- Supports constitutionally diverse assemblies and conformationally diverse ensembles
- Captures definitions for spatial restraints derived from different kinds of experimental techniques
- Provides a generic representation for referencing related data from external resources via stable identifiers
- Incorporates simplified definitions of the modeling workflow
The IHMCIF dictionary is developed as a collaborative project that is distributed freely through a public GitHub repository.
We have developed a new Data Harvesting System that provides a web interface for depositors to assemble all the information required for archiving integrative structures in PDB-Dev and to create a compliant mmCIF file. This includes the submission of integrative structures, associated spatial restraints and starting models used, modeling protocols and metadata information (citations, authors, software, data in external repositories, reference sequence information etc.).
The data harvesting system provides an automated mechanism for collecting diverse and heterogeneous types of integrative structures and restraint data. The system has been developed using the DERIVA scientific asset management platform and is based on the definitions in the IHMCIF dictionary and the parent PDBx/mmCIF dictionary.
A User Guide has been created with documentation regarding creating accounts and submitting data.
The Team
The PDB-Dev project is being developed by a multi-disciplinary team of researchers and developers from Rutgers, the State University of New Jersey, University of California San Francisco, and University of Southern California.
In 2014, the wwPDB convened an Integrative/Hybrid Methods (IHM) Task Force and sponsored a Workshop held at the European Bioinformatics Institute (EBI). The purpose of the Workshop was to engage a community of experts to make recommendations for how to responsibly archive integrative structures.
A white paper was published (Sali et al., 2015) and two working groups were established: the Federation Working Group was to address the issues of data federation and the Model Working Group was tasked with helping set up the framework for model representation, validation, and visualization.
The members of the wwPDB integrative/hybrid methods task force, the Federation and Model Working Groups and the wwPDB members are listed below.
| Member | Affiliation |
|---|---|
| Paul Adams | Lawrence Berkeley National Laboratory |
| Alexandre Bonvin | Utrecht University |
| Wah Chiu | Stanford University |
| Matteo dal Peraro | Ecole Polytechnique Federale de Lausanne |
| Frank DiMaio | University of Washington |
| Tom Ferrin | RBVI, University of California San Francisco | Kay Grunewald | University of Oxford |
| Richard Henderson | MRC Laboratory of Molecular Biology |
| Gerhard Hummer | Max Planck Institute for Biophysics |
| Kenji Iwasaki | Osaka University |
| Graham Johnson | University of California San Francisco |
| Marc Marti-Renom | Centre for Genomic Regulation |
| Jens Meiler | Vanderbilt University |
| Gaetano Montelione | Rutgers University |
| Michael Nilges | Institut Pasteur |
| Ruth Nussinov | Tel Aviv University |
| Juri Rappsilber | University of Edinburgh |
| Randy Read | Cambridge University |
| Helen Saibil | University of London |
| Andrej Sali | University of California San Francisco |
| Gunnar Schroder | Forschungszentrum Julich |
| Torsten Schwede | University of Basel |
| Charles Schwieters | National Institutes of Health |
| Claus Seidel | Heinrich Heine University Dusseldorf |
| Dmitri Svergun | EMBL Hamburg |
| Maya Topf | Birkbeck, University of London |
| Jill Trewhella | University of Sydney |
| Helen Berman | Rutgers University |
| Stephen Burley | RCSB PDB, Rutgers University |
| Aleksandras Gutmanas | PDBe, EMBL-EBI |
| Gerard Kleywegt | PDBe, EMBL-EBI |
| Catherine Lawson | RCSB, Rutgers University |
| John Markley | BMRB, University of Wisconsin Madison |
| Haruki Nakamura | PDBj, Osaka University |
| Ardan Patwardhan | PDBe, EMBL-EBI |
| Eldon Ulrich | BMRB, University of Wisconsin Madison |
| Sameer Velankar | PDBe, EMBL-EBI |
| John Westbrook | RCSB PDB, Rutgers University |
| Member | Affiliation |
|---|---|
| Jill Trewhella (co-chair) | University of Sydney |
| Helen Berman (co-chair) | Rutgers University |
| Rudolph Aebersold | ETH Zurich |
| Nigel Kirby | Australian Synchrotron |
| Paul Adams | Lawrence Berkeley Laboratory |
| Gaetano Montelione | Rutgers University |
| Wah Chiu | Stanford University |
| George N. Phillips | Rice University |
| Bridget Carragher | New York Structural Biology Center |
| Juri Rappsilber | Wellcome Trust Center for Cell Biology |
| Claus Seidel | Heinrich Heine University |
| Geerten Vuister | University of Leicester |
| Dmitri Svergun | EMBL Hamburg |
| Member | Affiliation |
|---|---|
| Andrej Sali (co-chair) | University of California San Francisco |
| Torsten Schwede (co-chair) | University of Basel |
| Jens Meiler | Vanderbilt University |
| Gerhard Hummer | Max Planck Institute for Biophysics |
| Frank DiMaio | University of Washington |
| Emad Tajkhorshid | University of Illinois Urbana-Champaign |
| Alexandre Bonvin | Utrecht University |
| Frank Alber (External Advisor) | University of California Los Angeles |
| Member | Affiliation |
|---|---|
| Stephen Burley | RCSB PDB, Rutgers University |
| Jeffrey Hoch | BMRB, University of Connecticut |
| Genji Kurisu | PDBj, Osaka University |
| John Markley | BMRB, University of Wisconsin Madison |
| Sameer Velankar | PDBe, EMBL-EBI |
| Member | Affiliation |
|---|---|
| Brinda Vallat | RCSB, Rutgers University |
| John Westbrook | RCSB PDB, Rutgers University |
| Benjamin Webb | University of California San Francisco |
| Tom Goddard | RBVI, University of California San Francisco |
| Kumaran Baskaran | BMRB, University of Wisconsin Madison |
| John Stone | University of Illinois Urbana-Champaign |
| Ryan McGreevy | University of Illinois Urbana-Champaign |
| Rocco Moretti | Vanderbilt University |
| Aleksandras Gutmanas | PDBe, EMBL-EBI |
| John Berrisford | PDBe, EMBL-EBI |
| Juergen Haas | University of Basel |
| Juergen Koefinger | Max Planck Institute for Biophysics |
| Gert-Jan Bekker | PDBj, Osaka University |
The IHMCIF dictionary and the PDB-Dev prototype system have been developed based on the recommendations of wwPDB integrative/hybrid methods task force published in the white paper (Sali et al., 2015).
In 2019, a Workshop was held as a Biophysical Society (BPS) Satellite Meeting to assess progress and discuss further requirements for archiving integrative structures. The primary goal of the Workshop was to build consensus for addressing the challenges involved in creating common data standards, building methods for federated data exchange, and developing mechanisms for validating integrative structures. The summary of the Workshop and the recommendations that emerged are published in a recent white paper (Berman et al., 2019).
| Participant | Affiliation |
|---|---|
| Paul Adams | Lawrence Berkeley National Laboratory |
| Helen Berman | Rutgers University |
| Alexandre Bonvin | Utrecht University |
| Stephen Burley | RCSB PDB, Rutgers University |
| Bridget Carragher | New York Structural Biology Center |
| Wah Chiu | Stanford University |
| Frank DiMaio | University of Washington |
| Thomas Ferrin | University of California San Francisco |
| Margaret Gabanyi | Rutgers University |
| Thomas Goddard | University of California San Francisco |
| Patrick Griffin | The Scripps Research Institute Florida |
| Juergen Haas | University of Basel |
| Christian Hanke | Heinrich Heine University Dusseldorf |
| Jeffrey Hoch | BMRB, University of Connecticut |
| Gerhard Hummer | Max Planck Institute for Biophysics |
| Genji Kurisu | Osaka University |
| Catherine Lawson | RCSB, Rutgers University |
| Alexander Leitner | ETH Zurich |
| John Markley | BMRB, University of Wisconsin Madison |
| Jens Meiler | Vanderbilt University |
| Gaetano Montelione | Rutgers University |
| George Phillips Jr. | Rice University |
| Thomas Prisner | Goethe University Frankfurt |
| Juri Rappsilber | University of Edinburgh |
| Andrej Sali | University of California San Francisco |
| David Schriemer | University of Calgary |
| Torsten Schwede | University of Basel |
| Claus Seidel | Heinrich Heine University Dusseldorf |
| Timothy Strutzenberg | The Scripps Research Institute Florida |
| Dmitri Svergun | EMBL Hamburg |
| Emad Tajkhorshid | University of Illinois Urbana-Champaign |
| Jill Trewhella | University of Sydney |
| Brinda Vallat | RCSB, Rutgers University |
| Sameer Velankar | PDBe, EMBL-EBI |
| Geeten Vuister | University of Leicester |
| Benjamin Webb | University of California San Francisco |
| John Westbrook | RCSB PDB, Rutgers University |
| Kate White | University of Southern California |
Funding
PDB-Dev is currently funded by NSF awards DBI-2112966, DBI-2112967, and DBI-2112968.
Previously, development of the IHMCIF dictionary and the PDB-Dev prototype system were funded by NSF awards DBI-1519158, DBI-1756248, and DBI-1756250.
Publications
Vallat B et al., Acta Cryst. 2021; D77: 1486-1496. doi:10.1107/S2059798321010871
Berman HM et al., Structure. 2019 Dec 3; 27(12): 1745-1759. doi:10.1016/j.str.2019.11.002
Vallat B et al., J Biomol NMR. 2019 Jul; 73(6-7): 385-398. doi:10.1007/s10858-019-00264-2
Vallat B et al., Structure. 2018 Jun; 26(6):894-904. doi:10.1016/j.str.2018.03.011
Burley SK et al., Structure. 2017 Sep; 25(9):1317-1318. doi: 10.1016/j.str.2017.08.001
Sali A et al., Structure. 2015 Jul; 23(7):1156-1167. doi: 10.1016/j.str.2015.05.013
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