Volume 66, Issue 3 pp. 655-663
Research Article

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

Ryotaro Koike

Ryotaro Koike

Global Scientific Information and Computing Center, Tokyo Institute of Technology, Ookayama, Tokyo 152-8550, Japan

Institute for Bioinformatics Research and Development, Japan Science and Technology Agency, Japan

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Kengo Kinoshita

Kengo Kinoshita

Structure and Function of Biomolecules, SORST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan

Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

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Akinori Kidera

Corresponding Author

Akinori Kidera

International Graduate School of Arts and Sciences, Yokohama City University, Tsurumi, Yokohama 230-0045, Japan

Institute of Molecular Science, Okazaki, 444-8585, Japan

International Graduate School of Arts and Sciences, Yokohama City University, Tsurumi, Yokohama 230-0045, Japan===Search for more papers by this author
First published: 06 December 2006
Citations: 3

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. Proteins 2007. © 2006 Wiley-Liss, Inc.

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