Protocol

Homology Modeling

Volume 857 of the series Methods in Molecular Biology pp 331-350

Date:

Macromolecular Assembly Structures by Comparative Modeling and Electron Microscopy

  • Keren LaskerAffiliated withDepartment of Bioengineering and Therapeutic Sciences, University of California, San FranciscoDepartment of Pharmaceutical Chemistry, University of California, San FranciscoCalifornia Institute for Quantitative Biosciences (QB3), University of California, San FranciscoThe Blavatnik School of Computer Science, Tel-Aviv University Email author 
  • , Javier A. Velázquez-MurielAffiliated withDepartment of Bioengineering and Therapeutic Sciences, University of California, San FranciscoDepartment of Pharmaceutical Chemistry, University of California, San FranciscoCalifornia Institute for Quantitative Biosciences (QB3), University of California, San Francisco
  • , Benjamin M. WebbAffiliated withDepartment of Bioengineering and Therapeutic Sciences, University of California, San FranciscoDepartment of Pharmaceutical Chemistry, University of California, San FranciscoCalifornia Institute for Quantitative Biosciences (QB3), University of California, San Francisco
  • , Zheng YangAffiliated withResource for Biocomputing, Visualization, and Informatics, Department of Pharmaceutical Chemistry, University of California, San Francisco
  • , Thomas E. FerrinAffiliated withResource for Biocomputing, Visualization, and Informatics, Department of Pharmaceutical Chemistry, University of California, San Francisco
  • , Andrej SaliAffiliated withDepartment of Bioengineering and Therapeutic Sciences, University of California, San FranciscoDepartment of Pharmaceutical Chemistry, University of California, San FranciscoCalifornia Institute for Quantitative Biosciences (QB3), University of California, San Francisco Email author 

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Abstract

Advances in electron microscopy allow for structure determination of large biological machines at increasingly higher resolutions. A key step in this process is fitting component structures into the electron microscopy-derived density map of their assembly. Comparative modeling can contribute by providing atomic models of the components, via fold assignment, sequence–structure alignment, model building, and model assessment. All four stages of comparative modeling can also benefit from consideration of the density map. In this chapter, we describe numerous types of modeling problems restrained by a density map and available protocols for finding solutions. In particular, we provide detailed instructions for density map-guided modeling using the Integrative Modeling Platform (IMP), MODELLER, and UCSF Chimera.

Key words

Macromolecular complexes Electron microscopy Fitting Homology modeling Comparative modeling Integrative modeling Visualization Chimera MODELLER IMP