{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:49:35Z","timestamp":1778600975560,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"W1","license":[{"start":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T00:00:00Z","timestamp":1557705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM083107"],"award-info":[{"award-number":["GM083107"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM116960"],"award-info":[{"award-number":["GM116960"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI134678"],"award-info":[{"award-number":["AI134678"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI1564756"],"award-info":[{"award-number":["DBI1564756"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The LOMETS2 server (https:\/\/zhanglab.ccmb.med.umich.edu\/LOMETS\/) is an online meta-threading server system for template-based protein structure prediction. Although the server has been widely used by the community over the last decade, the previous LOMETS server no longer represents the state-of-the-art due to aging of the algorithms and unsatisfactory performance on distant-homology template identification. An extension of the server built on cutting-edge methods, especially techniques developed since the recent CASP experiments, is urgently needed. In this work, we report the recent advancements of the LOMETS2 server, which comprise a number of major new developments, including (i) new state-of-the-art threading programs, including contact-map-based threading approaches, (ii) deep sequence search-based sequence profile construction and (iii) a new web interface design that incorporates structure-based function annotations. Large-scale benchmark tests demonstrated that the integration of the deep profiles and new threading approaches into LOMETS2 significantly improve its structure modeling quality and template detection, where LOMETS2 detected 176% more templates with TM-scores &gt;0.5 than the previous LOMETS server for Hard targets that lacked homologous templates. Meanwhile, the newly incorporated structure-based function prediction helps extend the usefulness of the online server to the broader biological community.<\/jats:p>","DOI":"10.1093\/nar\/gkz384","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T07:08:20Z","timestamp":1556694500000},"page":"W429-W436","source":"Crossref","is-referenced-by-count":130,"title":["LOMETS2: improved meta-threading server for fold-recognition and structure-based function annotation for distant-homology proteins"],"prefix":"10.1093","volume":"47","author":[{"given":"Wei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-1324","authenticated-orcid":false,"given":"Chengxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiqige","family":"Wuyun","sequence":"additional","affiliation":[{"name":"Computer Science and Engineering Department, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Pearce","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"School of Computer Science and Engineering, Nanjing University of Science and Technology, Xiaolingwei 200, Nanjing 210094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"2019062808223475300_B1","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1073\/pnas.0407152101","article-title":"The protein structure prediction problem could be solved using the current PDB library","volume":"102","author":"Zhang","year":"2005","journal-title":"PNAS"},{"key":"2019062808223475300_B2","volume-title":"11th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction","author":"Dunbrack","year":"2014"},{"issue":"Suppl. 1","key":"2019062808223475300_B3","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/prot.25425","article-title":"Evaluation of the template-based modeling in CASP12","volume":"86","author":"Kryshtafovych","year":"2018","journal-title":"Proteins"},{"key":"2019062808223475300_B4","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.1073\/pnas.91.10.4436","article-title":"An evolutionary approach to folding small alpha-helical proteins that uses sequence information and an empirical guiding fitness function","volume":"91","author":"Bowie","year":"1994","journal-title":"PNAS"},{"key":"2019062808223475300_B5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/358086a0","article-title":"A new approach to protein fold recognition","volume":"358","author":"Jones","year":"1992","journal-title":"Nature"},{"key":"2019062808223475300_B6","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/1097-0134(20000815)40:3<343::AID-PROT10>3.0.CO;2-S","article-title":"Protein threading using PROSPECT: design and evaluation","volume":"40","author":"Xu","year":"2000","journal-title":"Proteins"},{"key":"2019062808223475300_B7","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/prot.20106","article-title":"Development and large scale benchmark testing of the PROSPECTOR_3 threading algorithm","volume":"56","author":"Skolnick","year":"2004","journal-title":"Proteins"},{"key":"2019062808223475300_B8","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1093\/bioinformatics\/btr350","article-title":"Improving protein fold recognition and template-based modeling by employing probabilistic-based matching between predicted one-dimensional structural properties of query and corresponding native properties of templates","volume":"27","author":"Yang","year":"2011","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B9","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/prot.21945","article-title":"MUSTER: Improving protein sequence profile-profile alignments by using multiple sources of structure information","volume":"72","author":"Wu","year":"2008","journal-title":"Proteins"},{"key":"2019062808223475300_B10","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1093\/bioinformatics\/btt578","article-title":"FFAS-3D: improving fold recognition by including optimized structural features and template re-ranking","volume":"30","author":"Xu","year":"2014","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B11","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/bioinformatics\/bti125","article-title":"Protein homology detection by HMM-HMM comparison","volume":"21","author":"Soding","year":"2005","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B12","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"2019062808223475300_B13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.sbi.2006.03.004","article-title":"Servers for protein structure prediction","volume":"16","author":"Fischer","year":"2006","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2019062808223475300_B14","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.sbi.2008.02.004","article-title":"Progress and challenges in protein structure prediction","volume":"18","author":"Zhang","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2019062808223475300_B15","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/bioinformatics\/btg124","article-title":"3D-Jury: a simple approach to improve protein structure predictions","volume":"19","author":"Ginalski","year":"2003","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B16","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1093\/nar\/gkm251","article-title":"LOMETS: a local meta-threading-server for protein structure prediction","volume":"35","author":"Wu","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2019062808223475300_B17","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/prot.10357","article-title":"3D-SHOTGUN: a novel, cooperative, fold-recognition meta-predictor","volume":"51","author":"Fischer","year":"2003","journal-title":"Proteins"},{"key":"2019062808223475300_B18","article-title":"Assessing template-based models","volume-title":"13th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction","author":"Croll","year":"2018"},{"key":"2019062808223475300_B19","doi-asserted-by":"crossref","first-page":"D1096","DOI":"10.1093\/nar\/gks966","article-title":"BioLiP: a semi-manually curated database for biologically relevant ligand-protein interactions","volume":"41","author":"Yang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2019062808223475300_B20","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"2019062808223475300_B21","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":"2019062808223475300_B22","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nmeth.1818","article-title":"HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment","volume":"9","author":"Remmert","year":"2011","journal-title":"Nat. Methods"},{"key":"2019062808223475300_B23","doi-asserted-by":"crossref","first-page":"D170","DOI":"10.1093\/nar\/gkw1081","article-title":"Uniclust databases of clustered and deeply annotated protein sequences and alignments","volume":"45","author":"Mirdita","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2019062808223475300_B24","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1186\/1471-2105-11-431","article-title":"Hidden Markov model speed heuristic and iterative HMM search procedure","volume":"11","author":"Johnson","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2019062808223475300_B25","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/bioinformatics\/btu739","article-title":"UniRef clusters: a comprehensive and scalable alternative for improving sequence similarity searches","volume":"31","author":"Suzek","year":"2015","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B26","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1038\/s41467-018-04964-5","article-title":"Clustering huge protein sequence sets in linear time","volume":"9","author":"Steinegger","year":"2018","journal-title":"Nat. Commun."},{"key":"2019062808223475300_B27","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/prot.20308","article-title":"Fold recognition by combining sequence profiles derived from evolution and from depth-dependent structural alignment of fragments","volume":"58","author":"Zhou","year":"2005","journal-title":"Proteins"},{"key":"2019062808223475300_B28","doi-asserted-by":"crossref","first-page":"e1004343","DOI":"10.1371\/journal.pcbi.1004343","article-title":"Automatic prediction of protein 3D structures by probabilistic multi-template homology modeling","volume":"11","author":"Meier","year":"2015","journal-title":"PLoS Comput. Biol."},{"key":"2019062808223475300_B29","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1093\/bioinformatics\/btn504","article-title":"Profile Comparer: a program for scoring and aligning profile hidden Markov models","volume":"24","author":"Madera","year":"2008","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B30","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/btz291","article-title":"ResPRE: high-accuracy protein contact prediction by coupling precision matrix with deep residual neural networks","author":"Li","year":"2019","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B31","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1093\/bioinformatics\/btu829","article-title":"3Dmol.js: molecular visualization with WebGL","volume":"31","author":"Rego","year":"2015","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B32","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."},{"issue":"Suppl. 2","key":"2019062808223475300_B33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/prot.24452","article-title":"Critical assessment of methods of protein structure prediction (CASP)\u2013round x","volume":"82","author":"Moult","year":"2014","journal-title":"Proteins"},{"key":"2019062808223475300_B34","doi-asserted-by":"crossref","first-page":"i263","DOI":"10.1093\/bioinformatics\/bty278","article-title":"Protein threading using residue co-variation and deep learning","volume":"34","author":"Zhu","year":"2018","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B35","first-page":"146","article-title":"Protein structure modeling by predicted distance instead of contacts","author":"Xu","year":"2018","journal-title":"CASP13 Abstract"},{"key":"2019062808223475300_B36","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1093\/bioinformatics\/btp536","article-title":"QuickGO: a web-based tool for Gene Ontology searching","volume":"25","author":"Binns","year":"2009","journal-title":"Bioinformatics"},{"key":"2019062808223475300_B37","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/nar\/28.1.304","article-title":"The ENZYME database in 2000","volume":"28","author":"Bairoch","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2019062808223475300_B38","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"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/47\/W1\/W429\/28879826\/gkz384.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T21:42:03Z","timestamp":1568929323000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/47\/W1\/W429\/5488533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,13]]},"references-count":38,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2019,5,13]]},"published-print":{"date-parts":[[2019,7,2]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkz384","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7,2]]},"published":{"date-parts":[[2019,5,13]]}}}