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Related Experiment Videos

Alignment of protein sequences by their profiles.

Marc A Marti-Renom1, M S Madhusudhan, Andrej Sali

  • 1Mission Bay Genentech Hall, University of California, San Francisco, San Francisco, CA 94143, USA. marcius@salilab.org

Protein Science : a Publication of the Protein Society
|March 27, 2004
PubMed
Summary

Improving protein sequence alignment accuracy is achieved by aligning multiple sequence alignments. This new method significantly enhances accuracy, reaching 56% compared to existing techniques.

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Structural Biology

Background:

  • Accurate protein sequence alignment is crucial for understanding protein function and evolution.
  • Existing methods struggle with low sequence identity alignments, limiting comparative modeling.
  • Incorporating related sequences into alignment can improve accuracy.

Purpose of the Study:

  • To optimize and benchmark an approach for improving protein sequence alignment accuracy.
  • To evaluate thirteen novel protocols for creating and comparing multiple sequence alignment profiles.
  • To compare the performance of new protocols against established sequence alignment methods.

Main Methods:

  • Implemented thirteen protocols for profile creation and comparison within MODELLER's SALIGN command.

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  • Utilized a test set of 200 pairwise, structure-based alignments with <40% sequence identity.
  • Benchmarked new protocols against methods like BLAST, PSI-BLAST, HMMs (SAM, LOBSTER), SEA, CLUSTALW, and COMPASS.

    • Main Results:

    • The best new protocols significantly outperformed all previously described methods.
    • The top protocol achieved 56% accuracy in correctly aligned residues.
    • This represents a substantial improvement over existing methods (e.g., 26%-50% accuracy).

    Conclusions:

    • The novel approach of aligning multiple sequence alignments substantially improves protein sequence alignment accuracy.
    • This method is particularly effective for alignments with low sequence identity.
    • The enhanced accuracy facilitates large-scale comparative protein structure modeling.