{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:26:03Z","timestamp":1778894763408,"version":"3.51.4"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: The analysis of co-evolving residues has been exhaustively evaluated for the prediction of intramolecular amino acid contacts in soluble proteins. Although a variety of different methods for the detection of these co-evolving residues have been developed, the fraction of correctly predicted contacts remained insufficient for their reliable application in the construction of structural models. Membrane proteins, which constitute between one-fourth and one-third of all proteins in an organism, were only considered in few individual case studies.<\/jats:p><jats:p>Results: We present the first general study of correlated mutations in \u03b1-helical membrane proteins. Using seven different prediction algorithms, we extracted co-evolving residues for 14 membrane proteins having a solved 3D structure. On average, distances between correlated pairs of residues lying on different transmembrane segments were found to be significantly smaller compared to a random prediction. Covariation of residues was frequently found in direct sequence neighborhood to helix\u2013helix contacts. Based on the results obtained from individual prediction methods, we constructed a consensus prediction for every protein in the dataset that combines obtained correlations from different prediction algorithms and simultaneously removes likely false positives. Using this consensus prediction, 53% of all predicted residue pairs were found within one helix turn of an observed helix\u2013helix contact. Based on the combination of co-evolving residues detected with the four best prediction algorithms, interacting helices could be predicted with a specificity of 83% and sensitivity of 42%.<\/jats:p><jats:p>Availability: \u00a0http:\/\/webclu.bio.wzw.tum.de\/helixcorr\/<\/jats:p><jats:p>Contact: \u00a0d.frishman@wzw.tum.de<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm515","type":"journal-article","created":{"date-parts":[[2007,12,7]],"date-time":"2007-12-07T13:58:05Z","timestamp":1197035885000},"page":"3312-3319","source":"Crossref","is-referenced-by-count":67,"title":["Co-evolving residues in membrane proteins"],"prefix":"10.1093","volume":"23","author":[{"given":"Angelika","family":"Fuchs","sequence":"first","affiliation":[{"name":"1 Department of Genome Oriented Bioinformatics, Technische Universit\u00e4t M\u00fcnchen, Wissenschaftszentrum Weihenstephan, 85350 Freising, Germany and 2Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Ramat Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio J.","family":"Martin-Galiano","sequence":"additional","affiliation":[{"name":"1 Department of Genome Oriented Bioinformatics, Technische Universit\u00e4t M\u00fcnchen, Wissenschaftszentrum Weihenstephan, 85350 Freising, Germany and 2Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Ramat Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matan","family":"Kalman","sequence":"additional","affiliation":[{"name":"1 Department of Genome Oriented Bioinformatics, Technische Universit\u00e4t M\u00fcnchen, Wissenschaftszentrum Weihenstephan, 85350 Freising, Germany and 2Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Ramat Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarel","family":"Fleishman","sequence":"additional","affiliation":[{"name":"1 Department of Genome Oriented Bioinformatics, Technische Universit\u00e4t M\u00fcnchen, Wissenschaftszentrum Weihenstephan, 85350 Freising, Germany and 2Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Ramat Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Ben-Tal","sequence":"additional","affiliation":[{"name":"1 Department of Genome Oriented Bioinformatics, Technische Universit\u00e4t M\u00fcnchen, Wissenschaftszentrum Weihenstephan, 85350 Freising, Germany and 2Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Ramat Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitrij","family":"Frishman","sequence":"additional","affiliation":[{"name":"1 Department of Genome Oriented Bioinformatics, Technische Universit\u00e4t M\u00fcnchen, Wissenschaftszentrum Weihenstephan, 85350 Freising, Germany and 2Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Ramat Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,12,15]]},"reference":[{"key":"2023041107272144200_","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1472-6807-6-13","article-title":"Prediction of transmembrane helix orientation in polytopic membrane proteins","volume":"6","author":"Adamian","year":"2006","journal-title":"BMC Struct. 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