{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T14:29:08Z","timestamp":1764858548220},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2220,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Earlier studies of protein structure revealed closed loops with a characteristic size 25\u201330 residues and ring-like shape as a basic universal structural element of globular proteins. Elementary functional loops (EFLs) have specific signatures and provide functional residues important for binding\/activation and principal chemical transformation steps of the enzymatic reaction. The goal of this work is to show how these functional loops evolved from pre-domain peptides and to find a set of prototypes from which the EFLs of contemporary proteins originated.<\/jats:p>\n               <jats:p>Results: This article describes a computational method for deriving prototypes of EFLs based on the sequences of complete genomes. The procedure comprises the iterative derivation of sequence profiles followed by their hierarchical clustering. The scoring function takes into account information content on profile positions, thus preserving the signature. The statistical significance of scores is evaluated from the empirical distribution of scores of the background model. A set of prototypes of EFLs from archaeal proteomes is derived. This set delineates evolutionary connections between major functions and illuminates how folds and functions emerged in pre-domain evolution as a combination of prototypes.<\/jats:p>\n               <jats:p>Contact: \u00a0Igor.Berezovsky@uni.no<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq374","type":"journal-article","created":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T17:41:46Z","timestamp":1283881306000},"page":"i497-i503","source":"Crossref","is-referenced-by-count":43,"title":["Prototypes of elementary functional loops unravel evolutionary connections between protein functions"],"prefix":"10.1093","volume":"26","author":[{"given":"Alexander","family":"Goncearenco","sequence":"first","affiliation":[{"name":"1 Computational Biology Unit, Bergen Center for Computational Science and 2Department of Informatics, University of Bergen, N-5008 Norway"},{"name":"1 Computational Biology Unit, Bergen Center for Computational Science and 2Department of Informatics, University of Bergen, N-5008 Norway"}]},{"given":"Igor N.","family":"Berezovsky","sequence":"additional","affiliation":[{"name":"1 Computational Biology Unit, Bergen Center for Computational Science and 2Department of Informatics, University of Bergen, N-5008 Norway"}]}],"member":"286","published-online":{"date-parts":[[2010,9,4]]},"reference":[{"key":"2023012508274037400_B1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/ng1482","article-title":"The \u2018evolvability\u2019 of promiscuous protein functions","volume":"37","author":"Aharoni","year":"2005","journal-title":"Nat. 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