{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:52:54Z","timestamp":1776131574878,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":3421,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: All residues in a protein are not equally important. Some are essential for the proper structure and function of the protein, whereas others can be readily replaced. Conservation analysis is one of the most widely used methods for predicting these functionally important residues in protein sequences.<\/jats:p><jats:p>Results: We introduce an information-theoretic approach for estimating sequence conservation based on Jensen\u2013Shannon divergence. We also develop a general heuristic that considers the estimated conservation of sequentially neighboring sites. In large-scale testing, we demonstrate that our combined approach outperforms previous conservation-based measures in identifying functionally important residues; in particular, it is significantly better than the commonly used Shannon entropy measure. We find that considering conservation at sequential neighbors improves the performance of all methods tested. Our analysis also reveals that many existing methods that attempt to incorporate the relationships between amino acids do not lead to better identification of functionally important sites. Finally, we find that while conservation is highly predictive in identifying catalytic sites and residues near bound ligands, it is much less effective in identifying residues in protein\u2013protein interfaces.<\/jats:p><jats:p>Availability: Data sets and code for all conservation measures evaluated are available at http:\/\/compbio.cs.princeton.edu\/conservation\/<\/jats:p><jats:p>Contact: \u00a0mona@cs.princeton.edu<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm270","type":"journal-article","created":{"date-parts":[[2007,5,23]],"date-time":"2007-05-23T17:31:07Z","timestamp":1179941467000},"page":"1875-1882","source":"Crossref","is-referenced-by-count":652,"title":["Predicting functionally important residues from sequence conservation"],"prefix":"10.1093","volume":"23","author":[{"given":"John A.","family":"Capra","sequence":"first","affiliation":[{"name":"Department of Computer Science and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA"}]},{"given":"Mona","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA"}]}],"member":"286","published-online":{"date-parts":[[2007,5,22]]},"reference":[{"key":"2023041105312549100_","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/nar\/28.1.304","article-title":"The enyzme database in 2000","volume":"28","author":"Bairoch","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023041105312549100_","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0022-2836(02)01036-7","article-title":"Analysis of catalytic residues in enzyme active sites","volume":"324","author":"Bartlett","year":"2002","journal-title":"J. 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