Structure Meeting Report Federating Structural Models and Data: Outcomes from A Workshop on Archiving Integrative Structures Helen M. Berman,1,2,3,* Paul D. Adams,4,5 Alexandre A. Bonvin,6 Stephen K. Burley,7,8,9,10 Bridget Carragher,11,12 Wah Chiu,13,14 Frank DiMaio,15 Thomas E. Ferrin,16 Margaret J. Gabanyi,8 Thomas D. Goddard,16 Patrick R. Griffin,17 Juergen Haas,18 Christian A. Hanke,19 Jeffrey C. Hoch,20 Gerhard Hummer,21,22 Genji Kurisu,23 Catherine L. Lawson,8 Alexander Leitner,24 John L. Markley,25 Jens Meiler,26 Gaetano T. Montelione,27,28,29 George N. Phillips, Jr.,30 (Author list continued on next page) 1Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA 2Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA 3Bridge Institute, Michelson Center, University of Southern California, Los Angeles, CA 90089, USA 4Physical Biosciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720-8235, USA 5Department of Bioengineering, University of California-Berkeley, Berkeley, CA 94720, USA 6Bijvoet Center for Biomolecular Research, Faculty of Science - Chemistry, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands 7Research Collaboratory for Structural Bioinformatics Protein Data Bank, The State University of New Jersey, Piscataway, NJ 08854, USA 8Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA 9Skaggs School of Pharmacy and Pharmaceutical Sciences and San Diego Supercomputer Center, University of California, San Diego, La Jolla, CA 92093, USA 10Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA 11Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY 10027, USA 12Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA 13Department of Bioengineering, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305-5447, USA 14SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA (Affiliations continued on next page) Structures of biomolecular systems are increasingly computed by integrative modeling. In this approach, a structural model is constructed by combining information from multiple sources, including varied experi- mental methods and prior models. In 2019, a Workshop was held as a Biophysical Society 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 stan- dards, building methods for federated data exchange, and developing mechanisms for validating integrative structures. The summary of the Workshop and the recommendations that emerged are presented here. Introduction The PDB has established a data-processing pipeline for When the Protein Data Bank (PDB) (Protein Data Bank, 1971) depositing, validating, archiving, and disseminating structures was first established in 1971, X-ray crystallography was the determined by single methods, and to a limited extent structures only method for determining three-dimensional structures of bio- based on data from two different experimental methods. Exam- logical macromolecules at sufficient resolution to build atomic ples of the latter include structures derived from a combination of models. A decade later, structures of biomolecules in solution X-ray crystallography plus neutron diffraction data, NMR, or X- could also be determined by nuclear magnetic resonance ray crystallography plus small-angle scattering (SAS) data. How- (NMR) spectroscopy (Williamson et al., 1985). Recently, three- ever, the processing of structures produced by integrating data dimensional cryoelectron microscopy (3DEM) (Henderson from many different methods and/or those depicted by non- et al., 1990) began to achieve unprecedented near-atomic reso- atomic, coarse-grained representations poses a greater chal- lution for large complex assemblies. Increasingly, investigators lenge. Given the importance of integrative structures for are also modeling structures based on data from more than advancing biological sciences and the significant investment one method (Rout and Sali, 2019). These integrative/hybrid made to determine them, the Worldwide Protein Data Bank approaches to structure determination consist of collecting in- (wwPDB) (Berman et al., 2003) initiated an effort to address the formation about a system using multiple experimental and key challenges in enhancing its data-processing pipeline to computational methods, followed by integrative/hybrid accommodate integrative structures. modeling that converts this information into integrative/hybrid In 2014, the wwPDB convened an Integrative/Hybrid structure models. For succinctness, we will use the term integra- Methods (IHM) Task Force and sponsored a Workshop held at tive hereafter to refer to integrative/hybrid approaches, the European Bioinformatics Institute (EBI). The purpose of the modeling, and models. Workshop was to engage a community of experts to make Structure 27, December 3, 2019 1745 Structure Meeting Report Thomas Prisner,31 Juri Rappsilber,32 David C. Schriemer,33 Torsten Schwede,18 Claus A.M. Seidel,19 Timothy S. Strutzenberg,17 Dmitri I. Svergun,34 Emad Tajkhorshid,35,36 Jill Trewhella,37,38 Brinda Vallat,8 Sameer Velankar,39 Geerten W. Vuister,40 Benjamin Webb,41 John D. Westbrook,7,8 Kate L. White,2,3 and Andrej Sali16,41,42,43,* 15Department of Biochemistry and Institute for Protein Design, University of Washington, Seattle, WA 98195, USA 16Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA 17The Scripps Research Institute, Jupiter, FL 33458, USA 18Swiss Institute of Bioinformatics and Biozentrum, University of Basel, 4056 Basel, Switzerland 19Molecular Physical Chemistry, Heinrich Heine University Dusseldorf,€ 40225 Dusseldorf,€ Germany 20Department of Molecular Biology and Biophysics, UConn Health, Farmington, CT 06030, USA 21Department of Theoretical Biophysics, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany 22Institute for Biophysics, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany 23Protein Data Bank Japan (PDBj), Institute for Protein Research, Osaka University, Osaka 565-0871, Japan 24Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland 25BioMagResBank (BMRB), Biochemistry Department, University of Wisconsin-Madison, Madison, WI 53706, USA 26Center for Structural Biology, Vanderbilt University, 465 21st Avenue South, Nashville, TN 37221, USA 27Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA 28Department of Biochemistry, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA 29Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytech Institute, Troy, NY 12180, USA 30BioSciences at Rice and Department of Chemistry, Rice University, Houston, TX 77251, USA 31Institute of Physical and Theoretical Chemistry and Center of Biomolecular Magnetic Resonance, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany 32Wellcome Trust Centre for Cell Biology, Edinburgh EH9 3JR, Scotland 33Department of Biochemistry & Molecular Biology, Robson DNA Science Centre, University of Calgary, Calgary, AB T2N 4N1, Canada 34European Molecular Biology Laboratory (EMBL), Hamburg Outstation, Notkestrasse 85, 22607 Hamburg, Germany 35Department of Biochemistry, NIH Center for Macromolecular Modeling and Bioinformatics, Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA 36Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA 37School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia 38Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA 39Protein Data Bank in Europe (PDBe), European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire CB10 1SD, UK 40Department of Molecular and Cell Biology, Leicester Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 9HN, UK 41Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA 42California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA 43Lead Contact *Correspondence: [email protected] (H.M.B.), [email protected] (A.S.) https://doi.org/10.1016/j.str.2019.11.002 recommendations for how to responsibly archive integrative address the issues of data federation (Figure 1) and the Model structures. The five recommendations formulated by the Work- Working Group was tasked with helping set up the framework shop participants were: for model representation, validation, and visualization. Over the last 5 years, steady progress has been made in imple- 1. In addition to archiving the models themselves, all relevant menting the IHM Task Force recommendations. Members of the experimental data and metadata as well as experimental Federation and Model Working Groups have met periodically in and computational