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 journalArticle

32 Citations (Scopus)

Abstract

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
Volume45
DOIs
StatePublished - Jul 5 2016
Externally publishedYes

Fingerprint

Macromolecular Substances
X ray crystallography
Computational methods
Viruses
Electron microscopy
Availability
Chromatophores
Capsid
X Ray Crystallography
Ribosomes
Electron Microscopy

Keywords

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

ASJC Scopus subject areas

  • Bioengineering
  • Structural Biology
  • Biophysics
  • Medicine(all)
  • Biochemistry
  • Cell Biology

Cite this

Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes. / Goh, Boon Chong; Hadden, Jodi A.; Bernardi, Rafael C.; Singharoy, Abhishek; McGreevy, Ryan; Rudack, Till; Cassidy, C. Keith; Schulten, Klaus.

In: Annual Review of Biophysics, Vol. 45, 05.07.2016, p. 253-278.

Research output: Contribution to journalArticle

Goh, Boon Chong ; Hadden, Jodi A. ; Bernardi, Rafael C. ; Singharoy, Abhishek ; McGreevy, Ryan ; Rudack, Till ; Cassidy, C. Keith ; Schulten, Klaus. / Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes. In: Annual Review of Biophysics. 2016 ; Vol. 45. pp. 253-278.
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