{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:50:53Z","timestamp":1792511453967,"version":"4.5.0"},"reference-count":57,"publisher":"Elsevier BV","issue":"20","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003766","name":"Ministerul Educa\u0163iei Na\u0163ionale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003766","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006730","name":"Ministry of Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006730","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.bpj.2026.09.015","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:05:20Z","timestamp":1789427120000},"page":"5921-5936","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conformational plasticity and sequence specificity interplay in noncanonical tandem RRM-RNA binding"],"prefix":"10.1016","volume":"125","author":[{"given":"Roxana Geanina","family":"Vasarhelyi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-3401","authenticated-orcid":false,"given":"Vlad","family":"Cojocaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bpj.2026.09.015_bib1","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2024.1454241","article-title":"RBPs: an RNA editor\u2019s choice","volume":"11","author":"Fierro-Monti","year":"2024","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.bpj.2026.09.015_bib2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molcel.2020.03.011","article-title":"How RNA-binding proteins interact with RNA: molecules and mechanisms","volume":"78","author":"Corley","year":"2020","journal-title":"Mol. Cell"},{"key":"10.1016\/j.bpj.2026.09.015_bib3","doi-asserted-by":"crossref","DOI":"10.1002\/wrna.1573","article-title":"The potential of engineered eukaryotic RNA-binding proteins as molecular tools and therapeutics","volume":"11","author":"Shotwell","year":"2020","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"10.1016\/j.bpj.2026.09.015_bib4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.biophys.27.1.407","article-title":"RNA recognition by RNP proteins during RNA processing","volume":"27","author":"Varani","year":"1998","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"10.1016\/j.bpj.2026.09.015_bib5","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1111\/j.1742-4658.2005.04650.x","article-title":"Protein families and RNA recognition","volume":"272","author":"Chen","year":"2005","journal-title":"FEBS J."},{"key":"10.1016\/j.bpj.2026.09.015_bib6","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nrg3813","article-title":"A census of human RNA-binding proteins","volume":"15","author":"Gerstberger","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.bpj.2026.09.015_bib7","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.sbi.2008.04.002","article-title":"RNA recognition motifs: boring? not quite","volume":"18","author":"Cl\u00e9ry","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.bpj.2026.09.015_bib8","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1101\/gad.13.9.1102","article-title":"Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA","volume":"13","author":"Ding","year":"1999","journal-title":"Genes Dev."},{"key":"10.1016\/j.bpj.2026.09.015_bib9","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1093\/emboj\/19.12.3132","article-title":"Structure of tandem RNA recognition motifs from polypyrimidine tract binding protein reveals novel features of the RRM fold","volume":"19","author":"Conte","year":"2000","journal-title":"EMBO J."},{"key":"10.1016\/j.bpj.2026.09.015_bib10","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/348515a0","article-title":"Crystal structure of the RNA-binding domain of the U1 small nuclear ribonucleoprotein A","volume":"348","author":"Nagai","year":"1990","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2026.09.015_bib11","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1111\/j.1742-4658.2005.04653.x","article-title":"The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression","volume":"272","author":"Maris","year":"2005","journal-title":"FEBS J."},{"key":"10.1016\/j.bpj.2026.09.015_bib12","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/372432a0","article-title":"Crystal structure at 1.92 \u00c5 resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin","volume":"372","author":"Oubridge","year":"1994","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2026.09.015_bib13","doi-asserted-by":"crossref","DOI":"10.1093\/database\/bay148","article-title":"RRMdb - an evolutionary-oriented database of RNA recognition motif sequences","volume":"2019","author":"Nowacka","year":"2019","journal-title":"Database"},{"key":"10.1016\/j.bpj.2026.09.015_bib14","article-title":"Analysis of the inter-domain orientation of tandem RRM domains with diverse linkers: connecting experimental with AlphaFold2 predicted models","volume":"6","author":"Roca-Mart\u00ednez","year":"2024","journal-title":"NAR Genom. Bioinf."},{"key":"10.1016\/j.bpj.2026.09.015_bib15","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/nsmb.2698","article-title":"Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43","volume":"20","author":"Lukavsky","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.09.015_bib16","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/cbic.201800645","article-title":"A small cyclic \u03b2-hairpin peptide mimics the Rbfox2 RNA recognition motif and binds to the precursor miRNA 20b","volume":"20","author":"Sun","year":"2019","journal-title":"Chembiochem"},{"key":"10.1016\/j.bpj.2026.09.015_bib17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/84131","article-title":"Structural basis for recognition of AU-rich element RNA by the HuD protein","volume":"8","author":"Wang","year":"2001","journal-title":"Nat. Struct. Biol."},{"key":"10.1016\/j.bpj.2026.09.015_bib18","doi-asserted-by":"crossref","first-page":"5892","DOI":"10.1038\/s41467-022-33552-x","article-title":"The solution structure of Dead End bound to AU-rich RNA reveals an unusual mode of tandem RRM-RNA recognition required for mRNA regulation","volume":"13","author":"Duszczyk","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bpj.2026.09.015_bib19","first-page":"181","article-title":"Dead end and detour: the function of the RNA-binding protein Dnd in posttranscriptional regulation in the germline","volume":"140","author":"Gross-Thebing","year":"2020"},{"key":"10.1016\/j.bpj.2026.09.015_bib20","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.devcel.2017.11.019","article-title":"The vertebrate protein Dead End maintains primordial germ cell fate by inhibiting somatic differentiation","volume":"43","author":"Gross-Thebing","year":"2017","journal-title":"Dev. Cell"},{"key":"10.1016\/j.bpj.2026.09.015_bib21","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/S0960-9822(03)00537-2","article-title":"Dead end, a novel vertebrate germplasm component, is required for zebrafish primordial germ cell migration and survival","volume":"13","author":"Weidinger","year":"2003","journal-title":"Curr. Biol."},{"key":"10.1016\/j.bpj.2026.09.015_bib22","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s11033-025-10325-5","article-title":"Dead-End protein expression, function, and mutation in cancer: a systematic review","volume":"52","author":"Faraji","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.bpj.2026.09.015_bib23","article-title":"In silico analysis of DND1 and its co-expressed genes in human cancers","volume":"29","author":"Zhang","year":"2022","journal-title":"Biochem. Biophys. Rep."},{"key":"10.1016\/j.bpj.2026.09.015_bib24","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.1038\/s41467-025-57490-6","article-title":"RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bpj.2026.09.015_bib25","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1038\/s44319-026-00781-w","article-title":"A Nanos3-containing protein complex can activate RNA translation in primordial germ cells in vivo","volume":"27","author":"Gupta","year":"2026","journal-title":"EMBO Rep."},{"key":"10.1016\/j.bpj.2026.09.015_bib26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s10565-024-09851-y","article-title":"Circular RNA CircFCHO2 (hsa_circ_0002490) promotes the proliferation of melanoma by directly binding to DND1","volume":"40","author":"Yang","year":"2024","journal-title":"Cell Biol. Toxicol."},{"key":"10.1016\/j.bpj.2026.09.015_bib27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2026.09.015_bib28","author":"Janin"},{"key":"10.1016\/j.bpj.2026.09.015_bib29","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1021\/acs.jcim.5c00969","article-title":"HADDOCK3: a modular and versatile platform for integrative modeling of biomolecular complexes","volume":"65","author":"Giulini","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.09.015_bib30","doi-asserted-by":"crossref","first-page":"5.6.1","DOI":"10.1002\/cpbi.3","article-title":"Comparative protein structure modeling using MODELLER","volume":"54","author":"Webb","year":"2016","journal-title":"Curr. Protoc. Bioinform."},{"key":"10.1016\/j.bpj.2026.09.015_bib32","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1021\/jz501780a","article-title":"Building water models: a different approach","volume":"5","author":"Izadi","year":"2014","journal-title":"J. Phys. Chem. Lett."},{"key":"10.1016\/j.bpj.2026.09.015_bib33","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1021\/acs.jctc.9b00591","article-title":"ff19SB: amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution","volume":"16","author":"Tian","year":"2020","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib34","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1021\/ct200162x","article-title":"Refinement of the Cornell et al. nucleic acids force field based on reference quantum chemical calculations of glycosidic torsion profiles","volume":"7","author":"Zgarbov\u00e1","year":"2011","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib35","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1021\/acs.jcim.3c01153","article-title":"AmberTools","volume":"63","author":"Case","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.09.015_bib36","doi-asserted-by":"crossref","DOI":"10.1063\/5.0014475","article-title":"Scalable molecular dynamics on CPU and GPU architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.bpj.2026.09.015_bib37","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib38","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1021\/ct700119m","article-title":"Clustering molecular dynamics trajectories: 1. characterizing the performance of different clustering algorithms","volume":"3","author":"Shao","year":"2007","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib39","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1021\/acs.biochem.2c00565","article-title":"Inter-domain flexibility of human Ser\/Arg-rich splicing factor 1 allows variable spacer length in cognate RNA's bipartite motifs","volume":"61","author":"De Silva","year":"2022","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2026.09.015_bib40","article-title":"The DND1\u2013NANOS3 complex shapes the primordial germ cell transcriptome via a heptanucleotide sequence in mRNA 3\u2032 UTRs","author":"Suzawa","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.bpj.2026.09.015_bib41","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1016\/j.bpj.2024.09.031","article-title":"RNA binding tunes the conformational plasticity and intradomain stability of TDP-43 tandem RNA recognition motifs","volume":"123","author":"Ozguney","year":"2024","journal-title":"Biophys. J."},{"key":"10.1016\/j.bpj.2026.09.015_bib42","doi-asserted-by":"crossref","first-page":"12690","DOI":"10.1073\/pnas.1303445110","article-title":"Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition","volume":"110","author":"Cl\u00e9ry","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2026.09.015_bib43","doi-asserted-by":"crossref","first-page":"7343","DOI":"10.1021\/acs.jpcb.2c05278","article-title":"Molecular dynamics simulations of protein RNA complexes by using an advanced electrostatic model","volume":"126","author":"Jing","year":"2022","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.09.015_bib44","doi-asserted-by":"crossref","DOI":"10.3389\/fchem.2023.1217506","article-title":"RNA-protein complexes and force field polarizability","volume":"11","author":"Baltrukevich","year":"2023","journal-title":"Front. Chem."},{"key":"10.1016\/j.bpj.2026.09.015_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.sbi.2022.102503","article-title":"Integrating experimental data with molecular simulations to investigate RNA structural dynamics","volume":"78","author":"Bernetti","year":"2023","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.bpj.2026.09.015_bib46","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1016\/j.bpj.2022.12.022","article-title":"The development of nucleic acids force fields: from an unchallenged past to a competitive future","volume":"122","author":"Liebl","year":"2023","journal-title":"Biophys. J."},{"key":"10.1016\/j.bpj.2026.09.015_bib47","first-page":"6831","article-title":"On the power and challenges of atomistic molecular dynamics to investigate RNA molecules","volume":"20","author":"Muscat","year":"2024","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib48","doi-asserted-by":"crossref","first-page":"4183","DOI":"10.1021\/acs.jctc.4c01357","article-title":"Can we ever develop an ideal RNA force field? lessons learned from simulations of the UUCG RNA tetraloop and other systems","volume":"21","author":"Ml\u00fdnsk\u00fd","year":"2025","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib49","doi-asserted-by":"crossref","first-page":"8423","DOI":"10.1021\/acs.jctc.3c00990","article-title":"Simple adjustment of intranucleotide base-phosphate interaction in the OL3 AMBER force field improves RNA simulations","volume":"19","author":"Ml\u00fdnsk\u00fd","year":"2023","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib50","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aar8521","article-title":"Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations","volume":"4","author":"Bottaro","year":"2018","journal-title":"Sci. Adv."},{"key":"10.1016\/j.bpj.2026.09.015_bib51","doi-asserted-by":"crossref","first-page":"7601","DOI":"10.1021\/acs.jctc.0c00801","article-title":"UUCG RNA tetraloop as a formidable force-field challenge for MD simulations","volume":"16","author":"Mr\u00e1zikov\u00e1","year":"2020","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2026.09.015_bib52","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1021\/acs.chemrev.7b00427","article-title":"RNA structural dynamics as captured by molecular simulations: a comprehensive overview","volume":"118","author":"\u0160poner","year":"2018","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bpj.2026.09.015_bib53","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1093\/nar\/gky221","article-title":"Influence of Na+ and Mg2+ ions on RNA structures studied with molecular dynamics simulations","volume":"46","author":"Fischer","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.09.015_bib54","doi-asserted-by":"crossref","first-page":"9058","DOI":"10.1021\/acs.jpcb.5c02586","article-title":"Critical role of Mg2+ ions in RNA folding transitions: anchoring the A-minor twist in the SAM-II riboswitch","volume":"129","author":"Viegas","year":"2025","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.09.015_bib55","doi-asserted-by":"crossref","first-page":"6452","DOI":"10.1093\/nar\/gkw438","article-title":"Synergy between NMR measurements and MD simulations of protein\/RNA complexes: application to the RRMs, the most common RNA recognition motifs","volume":"44","author":"Krepl","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.09.015_bib56","doi-asserted-by":"crossref","first-page":"12480","DOI":"10.1093\/nar\/gkac1106","article-title":"Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field","volume":"50","author":"Krepl","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.09.015_bib57","doi-asserted-by":"crossref","first-page":"9525","DOI":"10.1021\/acs.jpcb.2c06168","article-title":"Conformational heterogeneity of RNA stem-loop hairpins bound to FUS-RNA recognition motif with disordered RGG tail revealed by unbiased molecular dynamics simulations","volume":"126","author":"Pokorn\u00e1","year":"2022","journal-title":"J. Phys. Chem. B."},{"key":"10.1016\/j.bpj.2026.09.015_bib58","first-page":"161","article-title":"Molecular dynamics simulation of TDP-43 RRM in the presence and absence of RNA","volume":"7","author":"Scott","year":"2024","journal-title":"J. Bioinf. Syst. Biol."}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349526006454?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349526006454?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:25:08Z","timestamp":1792509908000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006349526006454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":57,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["S0006349526006454"],"URL":"https:\/\/doi.org\/10.1016\/j.bpj.2026.09.015","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Conformational plasticity and sequence specificity interplay in noncanonical tandem RRM-RNA binding","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bpj.2026.09.015","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc. on behalf of Biophysical Society.","name":"copyright","label":"Copyright"}]}}