Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes

Boon Chong Goh, Jodi A. Hadden, Rafael C. Bernardi, Abhishek Singharoy, Ryan McGreevy, Till Rudack, C. Keith Cassidy, Klaus Schulten

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


The rise of the computer as a powerful tool for model building and refinement has revolutionized the field of structure determination for large biomolecular systems. Despite the wide availability of robust experimental methods capable of resolving structural details across a range of spatiotemporal resolutions, computational hybrid methods have the unique ability to integrate the diverse data from multimodal techniques such as X-ray crystallography and electron microscopy into consistent, fully atomistic structures. Here, commonly employed strategies for computational real-space structural refinement are reviewed, and their specific applications are illustrated for several large macromolecular complexes: ribosome, virus capsids, chemosensory array, and photosynthetic chromatophore. The increasingly important role of computational methods in large-scale structural refinement, along with current and future challenges, is discussed.

Original languageEnglish (US)
Pages (from-to)253-278
Number of pages26
JournalAnnual review of biophysics
StatePublished - Jul 5 2016
Externally publishedYes


  • Cryo-EM
  • Flexible fitting
  • Hybrid methods
  • Integrative modeling
  • Molecular dynamics
  • Simulation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Bioengineering
  • Biochemistry
  • Cell Biology


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