{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:57:15Z","timestamp":1773662235101,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["771820"],"award-info":[{"award-number":["771820"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Most protein-structure superimposition tools consider only Cartesian coordinates. Yet, much of biology happens on the surface of proteins, which is why proteins with shared ancestry and similar function often have comparable surface shapes. Superposition of proteins based on surface shape can enable comparison of highly divergent proteins, identify convergent evolution and enable detailed comparison of surface features and binding sites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We present ZEAL, an interactive tool to superpose global and local protein structures based on their shape resemblance using 3D (Zernike-Canterakis) functions to represent the molecular surface. In a benchmark study of structures with the same fold, we show that ZEAL outperforms two other methods for shape-based superposition. In addition, alignments from ZEAL were of comparable quality to the coordinate-based superpositions provided by TM-align. For comparisons of proteins with limited sequence and backbone-fold similarity, where coordinate-based methods typically fail, ZEAL can often find alignments with substantial surface-shape correspondence. In combination with shape-based matching, ZEAL can be used as a general tool to study relationships between shape and protein function. We identify several categories of protein functions where global shape similarity is significantly more likely than expected by random chance, when comparing proteins with little similarity on the fold level. In particular, we find that global surface shape similarity is particular common among DNA binding proteins.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>ZEAL can be used online at https:\/\/andrelab.org\/zeal or as a standalone program with command line or graphical user interface. Source files and installers are available at https:\/\/github.com\/Andre-lab\/ZEAL.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab205","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T12:53:27Z","timestamp":1616676807000},"page":"2874-2881","source":"Crossref","is-referenced-by-count":11,"title":["ZEAL: protein structure alignment based on shape similarity"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7859-8047","authenticated-orcid":false,"given":"Filip","family":"Ljung","sequence":"first","affiliation":[{"name":"Division of Biochemistry and Structural Biology, Department of Chemistry, Lund University , Lund SE-22100, Sweden"}]},{"given":"Ingemar","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Division of Biochemistry and Structural Biology, Department of Chemistry, Lund University , Lund SE-22100, Sweden"}]}],"member":"286","published-online":{"date-parts":[[2021,3,27]]},"reference":[{"key":"2023061310562374600_btab205-B1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol"},{"key":"2023061310562374600_btab205-B2","doi-asserted-by":"crossref","first-page":"W565","DOI":"10.1093\/nar\/gkp405","article-title":"MolLoc: a web tool for the local structural alignment of molecular surfaces","volume":"37","author":"Angaran","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2023061310562374600_btab205-B3","doi-asserted-by":"crossref","first-page":"015003","DOI":"10.1088\/0965-0393\/20\/1\/015003","article-title":"Precipitate shape fitting and reconstruction by means of 3D Zernike functions","volume":"20","author":"Callahan","year":"2012","journal-title":"Modell. Simul. Mater. Sci. Eng"},{"key":"2023061310562374600_btab205-B4","first-page":"85","article-title":"3D Zernike moments and Zernike affine invariants for 3D image analysis and recognition","author":"Canterakis","year":"1999"},{"key":"2023061310562374600_btab205-B5","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1002\/prot.22715","article-title":"Real-time ligand binding pocket database search using local surface descriptors","volume":"78","author":"Chikhi","year":"2010","journal-title":"Proteins Struct. Funct. Bioinf"},{"key":"2023061310562374600_btab205-B6","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/S0969-2126(96)00119-0","article-title":"A structural explanation for the twilight zone of protein sequence homology","volume":"4","author":"Chung","year":"1996","journal-title":"Structure"},{"key":"2023061310562374600_btab205-B7","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1021\/jp212612t","article-title":"Fitting multimeric protein complexes into electron microscopy maps using 3D zernike descriptors","volume":"116","author":"Esquivel-Rodr\u00edguez","year":"2012","journal-title":"J. Phys. Chem. B"},{"key":"2023061310562374600_btab205-B8","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1002\/(SICI)1096-987X(19961115)17:14<1653::AID-JCC7>3.0.CO;2-K","article-title":"A fast method of molecular shape comparison: a simple application of a Gaussian description of molecular shape","volume":"17","author":"Grant","year":"1996","journal-title":"J. Comput. Chem"},{"key":"2023061310562374600_btab205-B9","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1089\/cmb.2008.0083","article-title":"The application of 3D zernike moments for the description of \u201cModel-Free\u201d molecular structure, functional motion, and structural reliability","volume":"16","author":"Grandison","year":"2009","journal-title":"J. Comput. Biol"},{"key":"2023061310562374600_btab205-B10","first-page":"125","volume-title":"Lecture Notes in Computer Science (Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), volume 5780 LNBI","author":"Gunasekaran","year":"2009"},{"key":"2023061310562374600_btab205-B11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1023\/A:1011255519438","article-title":"A radial basis function method for global optimization","volume":"19","author":"Gutmann","year":"2001","journal-title":"J. Global Optim"},{"key":"2023061310562374600_btab205-B12","doi-asserted-by":"crossref","first-page":"e1007970","DOI":"10.1371\/journal.pcbi.1007970","article-title":"Real time structural search of the Protein Data Bank","volume":"16","author":"Guzenko","year":"2020","journal-title":"PLoS Comput. Biol"},{"key":"2023061310562374600_btab205-B13","doi-asserted-by":"crossref","first-page":"e1006969","DOI":"10.1371\/journal.pcbi.1006969","article-title":"A global map of the protein shape universe","volume":"15","author":"Han","year":"2019","journal-title":"PLOS Comput. Biol"},{"key":"2023061310562374600_btab205-B14","first-page":"207","author":"Hanson","year":"2013"},{"key":"2023061310562374600_btab205-B23","first-page":"74","author":"Hawkins","year":"2007"},{"key":"2023061310562374600_btab205-B15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1021\/ci0342371","article-title":"SURFCOMP: a novel graph-based approach to molecular surface comparison","volume":"44","author":"Hofbauer","year":"2004","journal-title":"J. Chem. Inf. Comput. Sci"},{"key":"2023061310562374600_btab205-B16","first-page":"123","author":"Holm","year":"1993"},{"key":"2023061310562374600_btab205-B17","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gks435","article-title":"ProBiS-2012: web server and web services for detection of structurally similar binding sites in proteins","volume":"40","author":"Konc","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023061310562374600_btab205-B18","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1107\/S0108767313006016","article-title":"Three-dimensional single-particle imaging using angular correlations from X-ray laser data","volume":"69","author":"Liu","year":"2013","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr"},{"key":"2023061310562374600_btab205-B19","doi-asserted-by":"crossref","first-page":"W445","DOI":"10.1093\/nar\/gkq311","article-title":"HexServer: an FFT-based protein docking server powered by graphics processors","volume":"38","author":"Macindoe","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023061310562374600_btab205-B20","author":"Marsh","year":"2017"},{"key":"2023061310562374600_btab205-B21","volume-title":"Version 9.8 (R2020a)","year":"2020"},{"key":"2023061310562374600_btab205-B22","first-page":"216","author":"Novotni","year":"2003"},{"key":"2023061310562374600_btab205-B24","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/bioinformatics\/btu097","article-title":"ZDOCK server: interactive docking prediction of protein\u2013protein complexes and symmetric multimers","volume":"30","author":"Pierce","year":"2014","journal-title":"Bioinformatics"},{"key":"2023061310562374600_btab205-B25","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1287\/ijoc.1060.0182","article-title":"A stochastic radial basis function method for the global optimization of expensive functions","volume":"19","author":"Regis","year":"2007","journal-title":"INFORMS J. Comput"},{"key":"2023061310562374600_btab205-B27","first-page":"383","author":"Ritchie","year":"1999"},{"key":"2023061310562374600_btab205-B28","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1093\/bioinformatics\/btn334","article-title":"Accelerating and focusing protein-protein docking correlations using multi-dimensional rotational FFT generating functions","volume":"24","author":"Ritchie","year":"2008","journal-title":"Bioinformatics"},{"key":"2023061310562374600_btab205-B29","author":"Rost","year":"1999"},{"key":"2023061310562374600_btab205-B30","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1471-2105-11-S11-S2","article-title":"Improved protein surface comparison and application to low-resolution protein structure data","volume":"11","author":"Sael","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023061310562374600_btab205-B31","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/prot.22030","article-title":"Fast protein tertiary structure retrieval based on global surface shape similarity","volume":"72","author":"Sael","year":"2008","journal-title":"Proteins Struct. Funct. Bioinf"},{"key":"2023061310562374600_btab205-B32","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1021\/ci2002704","article-title":"Rapid shape-based ligand alignment and virtual screening method based on atom\/feature-pair similarities and volume overlap scoring","volume":"51","author":"Sastry","year":"2011","journal-title":"J. Chem. Inf. Model"},{"key":"2023061310562374600_btab205-B33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1023\/A:1012692601098","article-title":"Angles in complex vector spaces","volume":"69","author":"Scharnhorst","year":"2001","journal-title":"Acta Appl. Math"},{"key":"2023061310562374600_btab205-B34","doi-asserted-by":"crossref","first-page":"W363","DOI":"10.1093\/nar\/gki481","article-title":"PatchDock and SymmDock: servers for rigid and symmetric docking","volume":"33","author":"Schneidman-Duhovny","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023061310562374600_btab205-B35","author":"Shindyalov","year":"1998"},{"key":"2023061310562374600_btab205-B36","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12859-015-0874-8","article-title":"MS3ALIGN: an efficient molecular surface aligner using the topology of surface curvature","volume":"17","author":"Shivashankar","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"2023061310562374600_btab205-B37","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1093\/nar\/gky092","article-title":"UniProt: the universal protein knowledgebase","volume":"46","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2023061310562374600_btab205-B38","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1093\/bioinformatics\/btg224","article-title":"PISCES: a protein sequence culling server","volume":"19","author":"Wang","year":"2003","journal-title":"Bioinformatics"},{"key":"2023061310562374600_btab205-B39","doi-asserted-by":"crossref","first-page":"e8140","DOI":"10.1371\/journal.pone.0008140","article-title":"Generating triangulated macromolecular surfaces by euclidean distance transform","volume":"4","author":"Xu","year":"2009","journal-title":"PLoS One"},{"key":"2023061310562374600_btab205-B40","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1093\/bioinformatics\/btq066","article-title":"How significant is a protein structure similarity with TM-score = 0.5?","volume":"26","author":"Xu","year":"2010","journal-title":"Bioinformatics"},{"key":"2023061310562374600_btab205-B41","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 Struct. Funct. Genet"},{"key":"2023061310562374600_btab205-B42","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":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btab205\/37038249\/btab205.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/18\/2874\/50579398\/btab205.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/18\/2874\/50579398\/btab205.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T10:59:17Z","timestamp":1686653957000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/18\/2874\/6194581"}},"subtitle":[],"editor":[{"given":"Alfonso","family":"Valencia","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2021,3,27]]},"references-count":41,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2021,9,29]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btab205","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9,15]]},"published":{"date-parts":[[2021,3,27]]}}}