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Related Experiment Videos

Misleading local sequence alignments: implications for comparative protein modelling

M A Saqi1, R B Russell, M J Sternberg

  • 1Bioinformatics Group, Glaxo-Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK.

Protein Engineering
|September 28, 1998
PubMed
Summary
This summary is machine-generated.

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Misleading local sequence alignments (MLSAs) can occur in homologous proteins, even with high global sequence identity. This finding impacts protein modeling and function inference, especially when global identity is below 40%.

Area of Science:

  • Structural bioinformatics
  • Computational biology
  • Protein sequence analysis

Background:

  • Protein sequence similarity often correlates with structural similarity.
  • Misaligned regions in structural alignments are typically assumed to have low local sequence identity.
  • Recent research indicates exceptions where high local identity stretches are not structurally reflected.

Purpose of the Study:

  • To quantify the occurrence of misleading local sequence alignments (MLSAs) in homologous proteins.
  • To investigate the relationship between global sequence identity and the likelihood of MLSAs.
  • To assess the implications of MLSAs for protein modeling and function inference.

Main Methods:

  • Analysis of 290 pairs of homologous proteins.

Related Experiment Videos

  • Comparison of sequence-based alignments with structure-based alignments.
  • Quantification of local sequence identity within misaligned regions.
  • Main Results:

    • MLSAs were found to be likely when global sequence identity is less than 40%.
    • MLSAs can occur even when global sequence identity exceeds 60%.
    • The study quantifies the frequency of these structural discrepancies.

    Conclusions:

    • The assumption that low local identity explains all misalignments is challenged.
    • MLSAs have significant implications for automated homology modeling accuracy.
    • Inferences of protein function based on sequence comparison require careful consideration of potential MLSAs.