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Probabilistic alignment detects remote homology in a pair of protein sequences without homologous sequence information
Author(s) -
Koike Ryotaro,
Kinoshita Kengo,
Kidera Akinori
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21240
Subject(s) - probabilistic logic , structural alignment , computational biology , alignment free sequence analysis , homology (biology) , sequence alignment , protein superfamily , structural similarity , multiple sequence alignment , smith–waterman algorithm , amino acid , heuristic , homology modeling , biology , genetics , peptide sequence , computer science , gene , biochemistry , artificial intelligence , enzyme
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.