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 IHM 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 IHM Dictionary is developed as a collaborative project that is distributed freely through a public GitHub repository.

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.


Dr. Andrej Sali
UCSF
andrej.sali@rcsb.org
Dr. Helen M. Berman
Rutgers
helen.berman@rcsb.org
Dr. Brinda Vallat
Rutgers
brinda.vallat@rcsb.org


Dr. John Westbrook
Rutgers
john.westbrook@rcsb.org
Dr. Carl Kesselman
USC
carl@isi.edu
Dr. Benjamin Webb
UCSF
ben@salilab.org


Dr. Sai Ganesan
UCSF
ganesans@salilab.org
Dr. Ignacia Echeverria
UCSF
ignacia@salilab.org
Maryam Fayazi
Rutgers
maryam.fayazi@rcsb.org

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 IHM 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

The development of the IHM dictionary and the PDB-Dev prototype system have been funded by NSF awards DBI-1519158, DBI-1756248, and DBI-1756250.

Publications

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


For information on how to cite PDB-Dev, refer to the FAQ page.

Supported by
National Science Foundation