Determining macromolecular assembly structures by molecular docking and fitting into an electron density map

Keren Lasker, Andrej Sali, Haim J. Wolfson

Research output: Contribution to journalArticlepeer-review

Abstract

Structural models of macromolecular assemblies are instrumental for gaining a mechanistic understanding of cellular processes. Determining these structures is a major challenge for experimental techniques, such as X-ray crystallography, NMR spectroscopy and electron microscopy (EM). Thus, computational modeling techniques, including molecular docking, are required. The development of most molecular docking methods has so far been focused on modeling of binary complexes. We have recently introduced the MultiFit method for modeling the structure of a multisubunit complex by simultaneously optimizing the fit of the model into an EM density map of the entire complex and the shape complementarity between interacting subunits. Here, we report algorithmic advances of the MultiFit method that result in an efficient and accurate assembly of the input subunits into their density map. The successful predictions and the increasing number of complexes being characterized by EM suggests that the CAPRI challenge could be extended to include docking-based modeling of macromolecular assemblies guided by EM.

Original languageEnglish
Pages (from-to)3205-3211
Number of pages7
JournalProteins: Structure, Function and Bioinformatics
Volume78
Issue number15
DOIs
StatePublished - 15 Nov 2010

Keywords

  • Electron microscopy
  • Gaussian mixture model
  • Inference
  • Integrative modeling
  • Macromolecules
  • Point alignment
  • Symmetry

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