Probabilistic alignment detects remote homology in a pair of protein sequences without homologous sequence information

Ryotaro Koike, Kengo Kinoshita, Akinori Kidera

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Dynamic programming (DP) and its heuristic algorithms are the most fundamental methods for similarity searches of amino acid sequences. Their detection power has been improved by including supplemental information, such as homologous sequences in the profile method. Here, we describe a method, probabilistic alignment (PA), that gives improved detection power, but similarly to the original DP, uses only a pair of amino acid sequences. Receiver operating characteristic (ROC) analysis demonstrated that the PA method is far superior to BLAST, and that its sensitivity and selectivity approach to those of PSI-BLAST. Particularly for orphan proteins having few homologues in the database, PA exhibits much better performance than PSI-BLAST. On the basis of this observation, we applied the PA method to a homology search of two orphan proteins, Latexin and Resuscitation-promoting factor domain. Their molecular functions have been described based on structural similarities, but sequence homologues have not been identified by PSI-BLAST. PA successfully detected sequence homologues for the two proteins and confirmed that the observed structural similarities are the result of an evolutional relationship.

Original languageEnglish
Pages (from-to)655-663
Number of pages9
JournalProteins: Structure, Function and Genetics
Volume66
Issue number3
DOIs
Publication statusPublished - 2007 Feb 15
Externally publishedYes

Keywords

  • Dynamic programming
  • Orphan protein
  • Probabilistic alignment
  • Sequence comparison
  • Sequence profile

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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