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Integrative Structure Determination of Protein Assemblies by Satisfaction of Spatial Restraints

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Protein-protein Interactions and Networks

Part of the book series: Computational Biology ((COBO,volume 9))

Abstract

To understand the cell, we need to determine the structures of macromolecular assemblies, many of which consist of tens to hundreds of components. A great variety of experimental data can be used to characterize the assemblies at several levels of resolution, from atomic structures to component configurations. To maximize completeness, resolution, accuracy, precision and efficiency of the structure determination, a computational approach is needed that can use spatial information from a variety of experimental methods. We propose such an approach, defined by its three main components: a hierarchical representation of the assembly, a scoring function consisting of spatial restraints derived from experimental data, and an optimization method that generates structures consistent with the data. We illustrate the approach by determining the configuration of the 456 proteins in the nuclear pore complex from Baker’s yeast.

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Authors and Affiliations

  1. Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089-1340, USA

    Frank Alber

  2. Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY, 10021-6399, USA

    Brian T. Chait

  3. Laboratory of Cellular and Structural Biology, The Rockefeller University, 1230 York Avenue, New York, NY, 10021-6399, USA

    Michael P. Rout

  4. Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California at San Francisco, Byers Hall, Suite 503B, 1700 4th Street, San Francisco, CA, 94158-2330, USA

    Andrej Sali

Authors
  1. Frank Alber
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  2. Brian T. Chait
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  3. Michael P. Rout
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  4. Andrej Sali
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Corresponding author

Correspondence to Frank Alber .

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Editors and Affiliations

  1. National Institutes of Health, Bethesda, Maryland, USA

    Anna Panchenko  & Teresa Przytycka  & 

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Alber, F., Chait, B.T., Rout, M.P., Sali, A. (2008). Integrative Structure Determination of Protein Assemblies by Satisfaction of Spatial Restraints. In: Panchenko, A., Przytycka, T. (eds) Protein-protein Interactions and Networks. Computational Biology, vol 9. Springer, London. https://doi.org/10.1007/978-1-84800-125-1_6

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  • DOI: https://doi.org/10.1007/978-1-84800-125-1_6

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84800-124-4

  • Online ISBN: 978-1-84800-125-1

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