{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:48:13Z","timestamp":1758401293489},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: A number of methods have been developed to predict functional specificity determinants in protein families based on sequence information. Most of these methods rely on pre-defined functional subgroups. Manual subgroup definition is difficult because of the limited number of experimentally characterized subfamilies with differing specificity, while automatic subgroup partitioning using computational tools is a non-trivial task and does not always yield ideal results.<\/jats:p>\n               <jats:p>Results: We propose a new approach SPEL (specificity positions by evolutionary likelihood) to detect positions that are likely to be functional specificity determinants. SPEL, which does not require subgroup definition, takes a multiple sequence alignment of a protein family as the only input, and assigns a P-value to every position in the alignment. Positions with low P-values are likely to be important for functional specificity. An evolutionary tree is reconstructed during the calculation, and P-value estimation is based on a random model that involves evolutionary simulations. Evolutionary log-likelihood is chosen as a measure of amino acid distribution at a position. To illustrate the performance of the method, we carried out a detailed analysis of two protein families (LacI\/PurR and G protein \u03b1 subunit), and compared our method with two existing methods (evolutionary trace and mutual information based). All three methods were also compared on a set of protein families with known ligand-bound structures.<\/jats:p>\n               <jats:p>Availability: SPEL is freely available for non-commercial use. Its pre-compiled versions for several platforms and alignments used in this work are available at<\/jats:p>\n               <jats:p>Contact: \u00a0grishin@chop.swmed.edu.<\/jats:p>\n               <jats:p>Supplementary information: Supplementary materials are available at<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti766","type":"journal-article","created":{"date-parts":[[2005,11,9]],"date-time":"2005-11-09T02:58:08Z","timestamp":1131505088000},"page":"164-171","source":"Crossref","is-referenced-by-count":41,"title":["Prediction of functional specificity determinants from protein sequences using log-likelihood ratios"],"prefix":"10.1093","volume":"22","author":[{"given":"Jimin","family":"Pei","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center 2 \u00a0 2 \u00a0 \u00a0 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center 2 \u00a0 2 \u00a0 \u00a0 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa N.","family":"Kinch","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center 1 \u00a0 1 \u00a0 \u00a0 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick V.","family":"Grishin","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center 1 \u00a0 1 \u00a0 \u00a0 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA"},{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center 2 \u00a0 2 \u00a0 \u00a0 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,11,8]]},"reference":[{"key":"2023012408312119600_b1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1006\/jmbi.2001.4870","article-title":"Automated structure-based prediction of functional sites in proteins: applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking","volume":"311","author":"Aloy","year":"2001","journal-title":"J. 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