Sequence harmony: detecting functional specificity from alignments

K Anton Feenstra, Walter Pirovano, Klaas Krab, Jaap Heringa

Research output: Contribution to JournalArticleAcademicpeer-review

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Multiple sequence alignments are often used for the identification of key specificity-determining residues within protein families. We present a web server implementation of the Sequence Harmony (SH) method previously introduced. SH accurately detects subfamily specific positions from a multiple alignment by scoring compositional differences between subfamilies, without imposing conservation. The SH web server allows a quick selection of subtype specific sites from a multiple alignment given a subfamily grouping. In addition, it allows the predicted sites to be directly mapped onto a protein structure and displayed. We demonstrate the use of the SH server using the family of plant mitochondrial alternative oxidases (AOX). In addition, we illustrate the usefulness of combining sequence and structural information by showing that the predicted sites are clustered into a few distinct regions in an AOX homology model. The SH web server can be accessed at

Original languageEnglish
Pages (from-to)W495-8
JournalNucleic Acids Research
Issue numberWeb Server issue
Publication statusPublished - Jul 2007


  • Algorithms
  • Amino Acid Sequence
  • Amino Acids
  • Binding Sites
  • Computational Biology
  • Conserved Sequence
  • Membrane Transport Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Proteins
  • Sequence Alignment
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid
  • Software
  • Journal Article
  • Research Support, Non-U.S. Gov't


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