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Evolutionary transitions in protein fold space.

William R Taylor1

  • 1Division of Mathematical Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. wtaylor@nimr.mrc.ac.uk

Current Opinion in Structural Biology
|June 21, 2007
PubMed
Summary
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Classifying protein folds is challenging using simple comparisons. A comprehensive approach requires considering evolutionary processes and the genetic environment for accurate protein fold classification.

Area of Science:

  • Structural biology
  • Bioinformatics
  • Evolutionary biology

Background:

  • The number of known protein folds is nearing completion, necessitating effective classification methods.
  • Current pairwise comparison metrics may be insufficient for a satisfactory systematic classification of protein folds.

Purpose of the Study:

  • To evaluate the challenges in systematically classifying protein folds.
  • To explore alternative approaches beyond pairwise comparisons for protein fold classification.
  • To integrate evolutionary processes and genetic context into protein fold classification.

Main Methods:

  • Analysis of existing protein fold classification metrics.
  • Proposal of a 'template' fold library approach.
  • Incorporation of evolutionary models and genetic factors (introns, gene fixation, population size).

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Main Results:

  • Pairwise comparison metrics are likely inadequate for comprehensive protein fold classification.
  • Comparison against idealized 'template' folds offers partial progress.
  • Unexpected evolutionary relationships among folds, such as circular permutations, highlight classification complexities.

Conclusions:

  • A robust protein fold classification system must incorporate evolutionary processes.
  • The genetic environment significantly complicates classification, requiring consideration of factors like introns and gene fixation.
  • Future classification efforts should integrate structural, evolutionary, and genetic data for a complete understanding.