Modeling of Proteins and Their Assemblies with the Integrative Modeling Platform

  • Benjamin Webb
  • Keren Lasker
  • Javier Velázquez-Muriel
  • Dina Schneidman-Duhovny
  • Riccardo Pellarin
  • Massimiliano Bonomi
  • Charles Greenberg
  • Barak Raveh
  • Elina Tjioe
  • Daniel Russel
  • Andrej Sali
Part of the Methods in Molecular Biology book series (MIMB, volume 1091)


To understand the workings of the living cell, we need to characterize protein assemblies that constitute the cell (for example, the ribosome, 26S proteasome, and the nuclear pore complex). A reliable high-resolution structural characterization of these assemblies is frequently beyond the reach of current experimental methods, such as X-ray crystallography, NMR spectroscopy, electron microscopy, footprinting, chemical cross-linking, FRET spectroscopy, small angle X-ray scattering, and proteomics. However, the information garnered from different methods can be combined and used to build models of the assembly structures that are consistent with all of the available datasets, and therefore more accurate, precise, and complete. Here, we describe a protocol for this integration, whereby the information is converted to a set of spatial restraints and a variety of optimization procedures can be used to generate models that satisfy the restraints as well as possible. These generated models can then potentially inform about the precision and accuracy of structure determination, the accuracy of the input datasets, and further data generation. We also demonstrate the Integrative Modeling Platform (IMP) software, which provides the necessary computational framework to implement this protocol, and several applications for specific use cases.

Key words

Integrative modeling Protein structure modeling Proteomics of macromolecular assemblies X-ray crystallography Electron microscopy SAXS 



We are grateful to all members of our research group, especially to Frank Alber, Friedrich Förster, and Bret Peterson who contributed to early versions of IMP, and Marc Marti-Renom, Davide Baù, Benjamin Schwarz, and Yannick Spill who currently contribute to IMP. We also acknowledge support from National Institutes of Health (R01 GM54762, U54 RR022220, PN2 EY016525, and R01 GM083960) as well as computing hardware support from Ron Conway, Mike Homer, Hewlett-Packard, NetApp, IBM, and Intel.


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Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  • Benjamin Webb
    • 1
  • Keren Lasker
    • 2
  • Javier Velázquez-Muriel
    • 2
  • Dina Schneidman-Duhovny
    • 2
  • Riccardo Pellarin
    • 2
  • Massimiliano Bonomi
    • 3
  • Charles Greenberg
    • 2
  • Barak Raveh
    • 2
  • Elina Tjioe
    • 2
  • Daniel Russel
    • 2
  • Andrej Sali
    • 2
  1. 1.Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quanstitative Biosciences (QB3)University of California San FranciscoSan FranciscoUSA
  2. 2.Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3)University of California San FranciscoSan FranciscoUSA
  3. 3.Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry and California Institute for Quantitative Biosciences (QB3)University of California San FranciscoSan FranciscoUSA

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