FOLD-EM: Automated fold recognition in medium-and low-resolution (4-15 Å) electron density maps

Mitul Saha, Marc Morais

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Motivation: Owing to the size and complexity of large multi-component biological assemblies, the most tractable approach to determining their atomic structure is often to fit high-resolution radiographic or nuclear magnetic resonance structures of isolated components into lower resolution electron density maps of the larger assembly obtained using cryo-electron microscopy (cryo-EM). This hybrid approach to structure determination requires that an atomic resolution structure of each component, or a suitable homolog, is available. If neither is available, then the amount of structural information regarding that component is limited by the resolution of the cryo-EM map. However, even if a suitable homolog cannot be identified using sequence analysis, a search for structural homologs should still be performed because structural homology often persists throughout evolution even when sequence homology is undetectable, As macromolecules can often be described as a collection of independently folded domains, one way of searching for structural homologs would be to systematically fit representative domain structures from a protein domain database into the medium/low resolution cryo-EM map and return the best fits. Taken together, the best fitting non-overlapping structures would constitute a 'mosaic' backbone model of the assembly that could aid map interpretation and illuminate biological function.Result: Using the computational principles of the Scale-Invariant Feature Transform (SIFT), we have developed FOLD-EM-a computational tool that can identify folded macromolecular domains in medium to low resolution (4-15 Å) electron density maps and return a model of the constituent polypeptides in a fully automated fashion. As a by-product, FOLD-EM can also do flexible multi-domain fitting that may provide insight into conformational changes that occur in macromolecular assemblies.Availability and implementation: FOLD-EM is available at: http://cs.stanford.edu/∼mitul/foldEM/, as a free open source software to the structural biology scientific community.

Original languageEnglish (US)
Pages (from-to)3265-3273
Number of pages9
JournalBioinformatics
Volume28
Issue number24
DOIs
StatePublished - Dec 2012

Fingerprint

Cryoelectron Microscopy
Carrier concentration
Fold
Electrons
Electron
Electron Microscopy
Electron microscopy
Protein Databases
Sequence Homology
Sequence Analysis
Homology
Magnetic Resonance Spectroscopy
Software
Polypeptides
Peptides
Macromolecules
Nuclear Magnetic Resonance
Open Source Software
Scale Invariant Feature Transform
Byproducts

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability
  • Medicine(all)

Cite this

FOLD-EM : Automated fold recognition in medium-and low-resolution (4-15 Å) electron density maps. / Saha, Mitul; Morais, Marc.

In: Bioinformatics, Vol. 28, No. 24, 12.2012, p. 3265-3273.

Research output: Contribution to journalArticle

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