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Related Experiment Videos

Predicting enzyme function from sequence: a systematic appraisal

I Shah1, L Hunter

  • 1Computational Sciences and Informatics, George Mason University, Fairfax, VA 22030, USA. ishah@gmu.edu

Proceedings. International Conference on Intelligent Systems for Molecular Biology
|January 1, 1997
PubMed
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Sequence similarity alone struggles to accurately classify proteins into Enzyme Commission (EC) functional classes. Focusing on protein domains, not whole sequences, is crucial for reliable functional assignment.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Enzymology

Background:

  • Accurate protein functional classification is vital for understanding biological processes.
  • The International Enzyme Commission (EC) provides a hierarchical system for enzyme classification.
  • Sequence similarity is a common approach for inferring protein function.

Purpose of the Study:

  • To evaluate the effectiveness of sequence alignment methods for classifying proteins into EC functional classes.
  • To determine if sequence similarity can reliably assign proteins to their correct EC categories.
  • To identify limitations and potential improvements in sequence-based functional assignment.

Main Methods:

  • Tested gapped and ungapped sequence alignment for protein classification.

Related Experiment Videos

  • Analyzed 15,208 proteins across 1,327 EC classes from the SwissProt database.
  • Utilized Receiver Operating Characteristic (ROC) statistics to assess similarity thresholds.

    • Main Results:

    • Approximately 60% of EC classes with multiple proteins could not be perfectly discriminated by sequence similarity.
    • False positive matches were prevalent, stemming from factors like multidomain proteins and convergent evolution.
    • Many 'false positives' represent biologically relevant functional assignments.

    Conclusions:

    • Sequence similarity alone is insufficient for precise functional classification of many enzymes.
    • Protein functional assignment should prioritize identifying and analyzing functionally significant domains.
    • Future efforts should focus on domain-level analysis for more accurate EC class assignment.