A core-weighted fitting method for docking atomic structures into low-resolution maps: Application to cryo-electron microscopy

Xiongwu Wu, Jacqueline L S Milne, Mario J. Borgnia, Alexey V. Rostapshov, Sriram Subramaniam, Bernard R. Brooks

Research output: Contribution to journalArticle

Abstract

Cryo-electron microscopy of "single particles" is a powerful method to analyze structures of large macromolecular assemblies that are not amenable to investigation by traditional X-ray crystallographic methods. A key step in these studies is to obtain atomic interpretations of multiprotein complexes by fitting atomic structures of individual components into maps obtained from electron microscopic data. Here, we report the use of a "core-weighting" method, combined with a grid-threading Monte Carlo (GTMC) approach for this purpose. The "core" of an individual structure is defined to represent the part where the density distribution is least likely to be altered by other components that comprise the macromolecular assembly of interest. The performance of the method has been evaluated by its ability to determine the correct fit of (i) the α-chain of the T-cell receptor variable domain into a simulated map of the αβ complex at resolutions between 5 and 40Å, and (ii) the E2 catalytic domain of the pyruvate dehydrogenase into an experimentally determined map, at 14Å resolution, of the icosahedral complex formed by 60 copies of this enzyme. Using the X-ray structures of the two test cases as references, we demonstrate that, in contrast to more traditional methods, the combination of the core-weighting method and the grid-threading Monte Carlo approach can identify the correct fit reliably and rapidly from the low-resolution maps that are typical of structures determined with the use of single-particle electron microscopy.

Original languageEnglish (US)
Pages (from-to)63-76
Number of pages14
JournalJournal of Structural Biology
Volume141
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Conformational search
  • Correlation function
  • Cryo-electron microscopy
  • Docking
  • Monte Carlo
  • Multiprotein complex
  • Single-particle microscopy

ASJC Scopus subject areas

  • Structural Biology

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