{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:25:36Z","timestamp":1771025136174,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: During the evolution, functional sites on the surface of the protein as well as the hydrophobic core maintaining the structural integrity are well-conserved. However, available protein structure alignment methods align protein structures based solely on the 3D geometric similarity, limiting their ability to detect functionally relevant correspondences between the residues of the proteins, especially for distantly related homologous proteins.<\/jats:p>\n               <jats:p>Results: In this article, we propose a new protein pairwise structure alignment algorithm (UniAlign) that incorporates additional evolutionary information captured in the form of sequence similarity, sequence profiles and residue conservation. We define a per-residue score (UniScore) as a weighted sum of these and other features and develop an iterative optimization procedure to search for an alignment with the best overall UniScore. Our extensive experiments on CDD, HOMSTRAD and BAliBASE benchmark datasets show that UniAlign outperforms commonly used structure alignment methods. We further demonstrate UniAlign's ability to develop family-specific models to drastically improve the quality of the alignments.<\/jats:p>\n               <jats:p>Availability and implementation: UniAlign is available as a web service at: http:\/\/sacan.biomed.drexel.edu\/unialign<\/jats:p>\n               <jats:p>Contact: \u00a0ahmet.sacan@drexel.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv354","type":"journal-article","created":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T04:09:00Z","timestamp":1433995740000},"page":"3139-3146","source":"Crossref","is-referenced-by-count":8,"title":["UniAlign: protein structure alignment meets evolution"],"prefix":"10.1093","volume":"31","author":[{"given":"Chunyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Center for Integrated Bioinformatics, School of Biomedical Engineering, Science and Health System, Drexel University, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet","family":"Sacan","sequence":"additional","affiliation":[{"name":"Center for Integrated Bioinformatics, School of Biomedical Engineering, Science and Health System, Drexel University, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,6,9]]},"reference":[{"key":"2023020202303236400_btv354-B1","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"2023020202303236400_btv354-B2","doi-asserted-by":"crossref","first-page":"D189","DOI":"10.1093\/nar\/gkh034","article-title":"The ASTRAL Compendium in 2004","volume":"32","author":"Chandonia","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023020202303236400_btv354-B3","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1529\/biophysj.105.066654","article-title":"Gaussian-weighted RMSD superposition of proteins: a structural comparison for flexible proteins and predicted protein structures","volume":"90","author":"Damm","year":"2006","journal-title":"Biophys. J."},{"key":"2023020202303236400_btv354-B4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/1471-2105-13-259","article-title":"Formatt: Correcting protein multiple structural alignments by incorporating sequence alignment","volume":"13","author":"Daniels","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"2023020202303236400_btv354-B5","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1093\/bioinformatics\/bth090","article-title":"A comparison of scoring functions for protein sequence profile alignment","volume":"20","author":"Edgar","year":"2004","journal-title":"Bioinformatics"},{"key":"2023020202303236400_btv354-B6","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/pro.5560070226","article-title":"Comprehensive assessment of automatic structural alignment against a manual standard, the scop classification of proteins","volume":"7","author":"Gerstein","year":"1998","journal-title":"Protein Sci."},{"key":"2023020202303236400_btv354-B7","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1107\/S0021889810030256","article-title":"Jmol - a paradigm shift in crystallographic visualization","volume":"43","author":"Hanson","year":"2010","journal-title":"J. Appl. Crystallogr."},{"key":"2023020202303236400_btv354-B8","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.sbi.2009.04.003","article-title":"Advances and pitfalls of protein structural alignment","volume":"19","author":"Hasegawa","year":"2009","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2023020202303236400_btv354-B9","doi-asserted-by":"crossref","first-page":"10915","DOI":"10.1073\/pnas.89.22.10915","article-title":"Amino acid substitution matrices from protein blocks","volume":"89","author":"Henikoff","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023020202303236400_btv354-B10","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1093\/bioinformatics\/btn507","article-title":"Searching protein structure databases with DaliLite v.3","volume":"24","author":"Holm","year":"2008","journal-title":"Bioinformatics"},{"key":"2023020202303236400_btv354-B11","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/protein\/13.8.535","article-title":"Protein structure alignment using environmental profiles","volume":"13","author":"Jung","year":"2000","journal-title":"Protein Eng."},{"key":"2023020202303236400_btv354-B12","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1107\/S0567739478001680","article-title":"A discussion of the solution for the best rotation to relate two sets of vectors","volume":"34","author":"Kabsch","year":"1978","journal-title":"Acta Crystallogr A"},{"key":"2023020202303236400_btv354-B13","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/bip.360221211","article-title":"Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features","volume":"22","author":"Kabsch","year":"1983","journal-title":"Biopolymers"},{"key":"2023020202303236400_btv354-B14","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/1471-2105-8-355","article-title":"Accuracy of structure-based sequence alignment of automatic methods","volume":"8","author":"Kim","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023020202303236400_btv354-B15","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.jmb.2004.12.032","article-title":"Comprehensive evaluation of protein structure alignment methods: scoring by geometric measures","volume":"346","author":"Kolodny","year":"2005","journal-title":"J. Mol. Biol."},{"key":"2023020202303236400_btv354-B16","doi-asserted-by":"crossref","first-page":"5913","DOI":"10.1073\/pnas.95.11.5913","article-title":"A unified statistical framework for sequence comparison and structure comparison","volume":"95","author":"Levitt","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023020202303236400_btv354-B17","doi-asserted-by":"crossref","first-page":"D348","DOI":"10.1093\/nar\/gks1243","article-title":"CDD: conserved domains and protein three-dimensional structure","volume":"41","author":"Marchler-Bauer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2023020202303236400_btv354-B18","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1110\/ps.051892906","article-title":"A comparative study of available software for high-accuracy homology modeling: from sequence alignments to structural models","volume":"15","author":"Nayeem","year":"2006","journal-title":"Protein Sci."},{"key":"2023020202303236400_btv354-B19","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/S0969-2126(97)00260-8","article-title":"CATH\u2013a hierarchic classification of protein domain structures","volume":"5","author":"Orengo","year":"1997","journal-title":"Structure"},{"key":"2023020202303236400_btv354-B20","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1186\/1471-2105-9-531","article-title":"Fr-TM-align: a new protein structural alignment method based on fragment alignments and the TM-score","volume":"9","author":"Pandit","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2023020202303236400_btv354-B21","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1186\/1471-2105-9-556","article-title":"The meaning of alignment: lessons from structural diversity","volume":"9","author":"Pirovano","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2023020202303236400_btv354-B22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/prot.340190108","article-title":"Combining evolutionary information and neural networks to predict protein secondary structure","volume":"19","author":"Rost","year":"1994","journal-title":"Proteins"},{"key":"2023020202303236400_btv354-B23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/prot.340090107","article-title":"Database of homology-derived protein structures and the structural meaning of sequence alignment","volume":"9","author":"Sander","year":"1991","journal-title":"Proteins"},{"key":"2023020202303236400_btv354-B24","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/(SICI)1097-0134(20000701)40:1<6::AID-PROT30>3.0.CO;2-7","article-title":"Large-scale comparison of protein sequence alignment algorithms with structure alignments","volume":"40","author":"Sauder","year":"2000","journal-title":"Proteins"},{"key":"2023020202303236400_btv354-B25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/prot.20665","article-title":"Optimization of multiple-sequence alignment based on multiple-structure alignment","volume":"62","author":"Shatsky","year":"2006","journal-title":"Proteins"},{"key":"2023020202303236400_btv354-B26","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/nar\/29.1.228","article-title":"A database and tools for 3-D protein structure comparison and alignment using the Combinatorial Extension (CE) algorithm","volume":"29","author":"Shindyalov","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2023020202303236400_btv354-B27","doi-asserted-by":"crossref","first-page":"D203","DOI":"10.1093\/nar\/gkh027","article-title":"HOMSTRAD: recent developments of the Homologous Protein Structure Alignment Database","volume":"32","author":"Stebbings","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023020202303236400_btv354-B28","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/prot.20527","article-title":"BAliBASE 3.0: latest developments of the multiple sequence alignment benchmark","volume":"61","author":"Thompson","year":"2005","journal-title":"Proteins"},{"key":"2023020202303236400_btv354-B29","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/prot.10146","article-title":"Scoring residue conservation","volume":"48","author":"Valdar","year":"2002","journal-title":"Proteins"},{"key":"2023020202303236400_btv354-B30","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1038\/srep01448","article-title":"Protein structure alignment beyond spatial proximity","volume":"3","author":"Wang","year":"2013","journal-title":"Sci. Rep."},{"key":"2023020202303236400_btv354-B31","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1038\/srep02619","article-title":"A comparative assessment and analysis of 20 representative sequence alignment methods for protein structure prediction","volume":"3","author":"Yan","year":"2013","journal-title":"Sci. Rep."},{"key":"2023020202303236400_btv354-B32","doi-asserted-by":"crossref","first-page":"ii246","DOI":"10.1093\/bioinformatics\/btg1086","article-title":"Flexible structure alignment by chaining aligned fragment pairs allowing twists","volume":"19","author":"Ye","year":"2003","journal-title":"Bioinformatics"},{"key":"2023020202303236400_btv354-B33","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/prot.20264","article-title":"Scoring function for automated assessment of protein structure template quality","volume":"57","author":"Zhang","year":"2004","journal-title":"Proteins"},{"key":"2023020202303236400_btv354-B34","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1093\/nar\/gki524","article-title":"TM-align: a protein structure alignment algorithm based on the TM-score","volume":"33","author":"Zhang","year":"2005","journal-title":"Nucleic Acids Res."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/19\/3139\/49035266\/bioinformatics_31_19_3139.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/19\/3139\/49035266\/bioinformatics_31_19_3139.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T03:49:38Z","timestamp":1675309778000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/19\/3139\/211984"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,9]]},"references-count":34,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2015,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv354","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,10,1]]},"published":{"date-parts":[[2015,6,9]]}}}