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Using CLUSTAL for multiple sequence alignments

D G Higgins1, J D Thompson, T J Gibson

  • 1European Molecular Biology Laboratory Outstation-European Bioinformatics Institute, Hinxton, Cambridge, United Kingdom.

Methods in Enzymology
|January 1, 1996
PubMed
Summary
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CLUSTAL W effectively aligns difficult protein sequences, especially with closely related data. New parameters improve loop region gap alignment, but users should explore options rather than trusting automatic results.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Multiple sequence alignment is crucial for understanding protein function and evolution.
  • Existing tools like CLUSTAL W face challenges with divergent sequences and complex alignment scenarios.
  • Parameter optimization is key to improving the accuracy of protein sequence alignments.

Purpose of the Study:

  • To evaluate the performance of CLUSTAL W in handling challenging protein alignment tasks.
  • To introduce and assess novel parameters designed to enhance gap placement in loop regions.
  • To guide users in effectively utilizing CLUSTAL W as a data exploration tool.

Main Methods:

  • Empirical testing of CLUSTAL W with diverse protein datasets, including globular and non-globular proteins.

Related Experiment Videos

  • Development and implementation of a new parameter set focusing on loop region gap encouragement.
  • Application of profile alignment options for sequential addition of divergent sequences, exemplified by SH2 domains.

    • Main Results:

    • CLUSTAL W demonstrates capability in aligning difficult protein sequences, particularly when initial datasets are highly related.
    • The new heuristic parameters significantly improve gap alignment in loop regions without compromising speed.
    • Profile alignment of SH2 domains showed superior results compared to a one-step full alignment, especially for divergent sequences.

    Conclusions:

    • CLUSTAL W is a powerful tool for protein sequence alignment, but parameter exploration is essential for optimal results.
    • The enhanced parameter set offers improved accuracy for challenging alignments, particularly in loop regions.
    • Users should treat CLUSTAL W as an exploratory tool, validating alignments with phylogenetic context and varied parameters.