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

Journal Article (Journal Article)

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 alpha-chain of the T-cell receptor variable domain into a simulated map of the alphabeta complex at resolutions between 5 and 40 A, and (ii) the E2 catalytic domain of the pyruvate dehydrogenase into an experimentally determined map, at 14 A 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.

Full Text

Duke Authors

Cited Authors

  • Wu, X; Milne, JLS; Borgnia, MJ; Rostapshov, AV; Subramaniam, S; Brooks, BR

Published Date

  • January 2003

Published In

Volume / Issue

  • 141 / 1

Start / End Page

  • 63 - 76

PubMed ID

  • 12576021

Pubmed Central ID

  • PMC6413516

International Standard Serial Number (ISSN)

  • 1047-8477

Digital Object Identifier (DOI)

  • 10.1016/s1047-8477(02)00570-1


  • eng

Conference Location

  • United States