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Practical limits of function prediction.

D Devos1, A Valencia

  • 1Protein Design Group, CNB-CSIC, Madrid, Spain.

Proteins
|August 16, 2000
PubMed
Summary
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Predicting protein function from sequence similarity is complex. While some functional aspects can be transferred, database errors and protein plasticity limit accuracy, especially at lower sequence identities.

Area of Science:

  • Biochemistry
  • Bioinformatics
  • Structural Biology

Background:

  • The increasing number of known protein sequences outpaces functional characterization.
  • Assigning protein function based on sequence similarity to known proteins is a common bioinformatics approach.

Purpose of the Study:

  • To critically evaluate the theoretical and practical basis of predicting protein function from sequence similarity.
  • To assess the reliability of transferring different functional aspects between homologous proteins.

Main Methods:

  • Analysis of true sequence similarities derived from structural alignments.
  • Investigation of various protein function facets: enzymatic classification, keyword annotations, cellular function, and binding site conservation.

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Main Results:

  • Transferring protein function based on sequence similarity is only moderately reliable.
  • Database inaccuracies and protein functional plasticity contribute to prediction limitations.
  • Empirical limits for pairwise functional annotation were established based on sequence identity thresholds for predicting protein fold descriptors, EC numbers, keywords, and binding sites.

Conclusions:

  • Predicting protein function solely from sequence similarity is challenging due to inherent complexities.
  • Reliable functional annotation requires careful consideration of sequence identity levels and potential functional divergence.