{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T14:13:41Z","timestamp":1771942421861,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1576,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The prediction of RNA 3D structures from its sequence only is a milestone to RNA function analysis and prediction. In recent years, many methods addressed this challenge, ranging from cycle decomposition and fragment assembly to molecular dynamics simulations. However, their predictions remain fragile and limited to small RNAs. To expand the range and accuracy of these techniques, we need to develop algorithms that will enable to use all the structural information available. In particular, the energetic contribution of secondary structure interactions is now well documented, but the quantification of non-canonical interactions\u2014those shaping the tertiary structure\u2014is poorly understood. Nonetheless, even if a complete RNA tertiary structure energy model is currently unavailable, we now have catalogues of local 3D structural motifs including non-canonical base pairings. A practical objective is thus to develop techniques enabling us to use this knowledge for robust RNA tertiary structure predictors.<\/jats:p>\n               <jats:p>Results: In this work, we introduce RNA-MoIP, a program that benefits from the progresses made over the last 30 years in the field of RNA secondary structure prediction and expands these methods to incorporate the novel local motif information available in databases. Using an integer programming framework, our method refines predicted secondary structures (i.e. removes incorrect canonical base pairs) to accommodate the insertion of RNA 3D motifs (i.e. hairpins, internal loops and k-way junctions). Then, we use predictions as templates to generate complete 3D structures with the MC-Sym program. We benchmarked RNA-MoIP on a set of 9 RNAs with sizes varying from 53 to 128 nucleotides. We show that our approach (i) improves the accuracy of canonical base pair predictions; (ii) identifies the best secondary structures in a pool of suboptimal structures; and (iii) predicts accurate 3D structures of large RNA molecules.<\/jats:p>\n               <jats:p>Availability: \u00a0RNA-MoIP is publicly available at: http:\/\/csb.cs.mcgill.ca\/RNAMoIP.<\/jats:p>\n               <jats:p>Contact: \u00a0jeromew@cs.mcgill.ca<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts226","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T14:09:18Z","timestamp":1339423758000},"page":"i207-i214","source":"Crossref","is-referenced-by-count":41,"title":["Towards 3D structure prediction of large RNA molecules: an integer programming framework to insert local 3D motifs in RNA secondary structure"],"prefix":"10.1093","volume":"28","author":[{"given":"Vladimir","family":"Reinharz","sequence":"first","affiliation":[{"name":"1 School of Computer Science & McGill Centre for Bioinformatics, McGill University H3A 0E9 and 2School of Computer Science & IRIC, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada H3C 2J7"}]},{"given":"Fran\u00e7ois","family":"Major","sequence":"additional","affiliation":[{"name":"1 School of Computer Science & McGill Centre for Bioinformatics, McGill University H3A 0E9 and 2School of Computer Science & IRIC, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada H3C 2J7"}]},{"given":"J\u00e9r\u00f4me","family":"Waldisp\u00fchl","sequence":"additional","affiliation":[{"name":"1 School of Computer Science & McGill Centre for Bioinformatics, McGill University H3A 0E9 and 2School of Computer Science & IRIC, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada H3C 2J7"}]}],"member":"286","published-online":{"date-parts":[[2012,6,9]]},"reference":[{"key":"2023012512360185100_B1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023012512360185100_B2","doi-asserted-by":"crossref","first-page":"D392","DOI":"10.1093\/nar\/gkm842","article-title":"RNAJunction: a database of RNA junctions and kissing loops for three-dimensional structural analysis and nanodesign","volume":"36","author":"Bindewald","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023012512360185100_B3","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nmeth.1603","article-title":"Sequence-based identification of 3D structural modules in RNA with RMDetect","volume":"8","author":"Cruz","year":"2011","journal-title":"Nat. Meth."},{"key":"2023012512360185100_B4","doi-asserted-by":"crossref","first-page":"14664","DOI":"10.1073\/pnas.0703836104","article-title":"Automated de novo prediction of native-like RNA tertiary structures","volume":"104","author":"Das","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023012512360185100_B5","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1261\/rna.1061108","article-title":"Automated motif extraction and classification in RNA tertiary structures","volume":"14","author":"Djelloul","year":"2008","journal-title":"RNA"},{"key":"2023012512360185100_B6","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1093\/bioinformatics\/btl246","article-title":"CONTRAfold: RNA secondary structure prediction without physics-based models","volume":"22","author":"Do","year":"2006","journal-title":"Bioinformatics"},{"key":"2023012512360185100_B7","doi-asserted-by":"crossref","first-page":"e1000406","DOI":"10.1371\/journal.pcbi.1000406","article-title":"A probabilistic model of RNA conformational space","volume":"5","author":"Frellsen","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2023012512360185100_B8","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1006\/jmbi.2001.4626","article-title":"Quantitative analysis of nucleic acid three-dimensional structures","volume":"308","author":"Gendron","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2023012512360185100_B9","doi-asserted-by":"crossref","DOI":"10.1002\/0471250953.bi1202s26","article-title":"RNA secondary structure analysis using the Vienna RNA package","volume-title":"Curr. Protoc. Bioinform.","author":"Hofacker","year":"2009"},{"key":"2023012512360185100_B10","volume-title":"Gurobi Optimization, I.","author":"Houston","year":"2011"},{"key":"2023012512360185100_B11","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1093\/bioinformatics\/btp576","article-title":"Knowledge-based instantiation of full atomic detail into coarse-grain RNA 3D structural models","volume":"25","author":"Jonikas","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012512360185100_B12","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1093\/bioinformatics\/btq321","article-title":"Assemble: an interactive graphical tool to analyze and build RNA architectures at the 2D and 3D levels","volume":"26","author":"Jossinet","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012512360185100_B13","doi-asserted-by":"crossref","first-page":"283101","DOI":"10.1088\/0953-8984\/22\/28\/283101","article-title":"Computational approaches to 3D modeling of RNA","volume":"22","author":"Laing","year":"2010","journal-title":"J. Phys. Condens. Matter"},{"key":"2023012512360185100_B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.compbiolchem.2011.11.001","article-title":"Automated prediction of three-way junction topological families in RNA secondary structures","volume":"37","author":"Lamiable","year":"2012","journal-title":"Comput. Biol. and Chem."},{"key":"2023012512360185100_B15","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1093\/nar\/gkf540","article-title":"RNA canonical and non-canonical base pairing types: a recognition method and complete repertoire","volume":"30","author":"Lemieux","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012512360185100_B16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-60327-429-6_1","article-title":"UNAFold: software for nucleic acid folding and hybridization","volume":"453","author":"Markham","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"2023012512360185100_B17","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1080\/07391102.2008.10531240","article-title":"RNA2D3D: a program for generating, viewing, and comparing 3-dimensional models of RNA","volume":"25","author":"Martinez","year":"2008","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2023012512360185100_B18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nature06684","article-title":"The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data","volume":"452","author":"Parisien","year":"2008","journal-title":"Nature"},{"issue":"Suppl. 1","key":"2023012512360185100_B19","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1186\/1471-2105-10-S1-S38","article-title":"Prediction of RNA secondary structure with pseudoknots using integer programming","volume":"10","author":"Poolsap","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2023012512360185100_B20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/1471-2105-11-129","article-title":"RNAstructure: software for RNA secondary structure prediction and analysis","volume":"11","author":"Reuter","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023012512360185100_B21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00285-007-0110-x","article-title":"FR3D: finding local and composite recurrent structural motifs in RNA 3D structures","volume":"56","author":"Sarver","year":"2008","journal-title":"J. Math. Biol."},{"key":"2023012512360185100_B22","doi-asserted-by":"crossref","first-page":"i85","DOI":"10.1093\/bioinformatics\/btr215","article-title":"IPknot: fast and accurate prediction of RNA secondary structures with pseudoknots using integer programming","volume":"27","author":"Sato","year":"2011","journal-title":"Bioinformatics"},{"key":"2023012512360185100_B23","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1093\/bioinformatics\/btn328","article-title":"iFoldRNA: three-dimensional RNA structure prediction and folding","volume":"24","author":"Sharma","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012512360185100_B24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-642-31265-6_26","article-title":"Impact of the energy model on the complexity of RNA folding with pseudoknots","volume-title":"Proceedings the 23rd Annual Symposium on Combinatorial Pattern Matching (CPM 2012).","author":"Sheik","year":"2012"},{"key":"2023012512360185100_B25","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1093\/nar\/gkp011","article-title":"Frequency and isostericity of RNA base pairs","volume":"37","author":"Stombaugh","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012512360185100_B26","doi-asserted-by":"crossref","first-page":"i102","DOI":"10.1093\/bioinformatics\/btr232","article-title":"A conditional random fields method for RNA sequence-structure relationship modeling and conformation sampling","volume":"27","author":"Wang","year":"2011","journal-title":"Bioinformatics"},{"key":"2023012512360185100_B27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1097-0282(199902)49:2<145::AID-BIP4>3.0.CO;2-G","article-title":"Complete suboptimal folding of RNA and the stability of secondary structures","volume":"49","author":"Wuchty","year":"1999","journal-title":"Biopolymers"},{"key":"2023012512360185100_B28","first-page":"546","article-title":"Rich parameterization improves rna structure prediction","author":"Zakov","year":"2011","journal-title":"RECOMB"},{"key":"2023012512360185100_B29","doi-asserted-by":"crossref","first-page":"i129","DOI":"10.1093\/bioinformatics\/btr220","article-title":"A folding algorithm for extended RNA secondary structures","volume":"27","author":"zu","year":"2011","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/12\/i207\/48883722\/bioinformatics_28_12_i207.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/12\/i207\/48883722\/bioinformatics_28_12_i207.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T16:25:00Z","timestamp":1674663900000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/12\/i207\/269345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,9]]},"references-count":29,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts226","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,6,15]]},"published":{"date-parts":[[2012,6,9]]}}}