Modeling of Proteins and Their Assemblies with the Integrative Modeling Platform

Benjamin Webb*, Keren Lasker, Dina Schneidman-Duhovny, Elina Tjioe, Jeremy Phillips, Seung Joong Kim, Javier Velázquez-Muriel, Daniel Russel, Andrej Sali

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

18 Scopus citations

Abstract

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 computational models of the assembly structures that are consistent with all of the available datasets. 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 much 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.

Original languageEnglish
Title of host publicationNetwork Biology
Subtitle of host publicationMethods and Applications
PublisherHumana Press Inc.
Pages377-397
Number of pages21
ISBN (Print)9781617792755
DOIs
StatePublished - 2011
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume781
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Bibliographical note

Publisher Copyright:
© 2011, Springer Science+Business Media, LLC.

Keywords

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

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