{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T22:59:55Z","timestamp":1781132395575,"version":"3.54.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The SARS-CoV-2 nucleocapsid protein (N), essential for viral RNA packaging, comprises a structured RNA-binding domain, NTD(44\u2013180), flanked by intrinsically disordered regions, IDR1 (1\u201343) and IDR2 (181\u2013248). This extended, positively charged RNA-binding surface makes it an attractive target for synthetic ligands able to interfere with its function. In this study, peptide ligands were explored as synthetically accessible alternatives for modulating N interactions. After confirming the ability of a reference peptide (P0) in engaging IDRs in the interaction, we shifted our attention to key properties that modulate the interaction with the central domain NTD(44\u2013180). Two new peptides (P1 and P2) were designed with identical amino acid compositions but distinct sequence arrangements. In each one a para-fluorinated phenylalanine residue was incorporated to introduce an aromatic component useful to mimic RNA bases and enable\n                    <jats:sup>19<\/jats:sup>\n                    F NMR detection. Molecular dynamics simulations, circular dichroism, and NMR spectroscopy were combined to characterize the structural, dynamic and binding properties of P1 and P2. Both peptides involve the RNA-binding groove of the N protein (NTD(44\u2013180)). While P1 demonstrated higher \u03b1-helical propensity and favorable electrostatic interactions, P2 displayed stronger interactions through enhanced conformational adaptability.\n                    <jats:sup>19<\/jats:sup>\n                    F NMR experiments confirmed complex formation also from the ligand perspective. These findings support a modular peptide design strategy for targeting multidomain proteins.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-46442-9","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T08:55:57Z","timestamp":1776502557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peptide ligands to explore interactions with intrinsically disordered multidomain proteins: the case of SARS-CoV-2 nucleocapsid protein"],"prefix":"10.1038","volume":"16","author":[{"given":"A. S.","family":"Tino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Quagliata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Schiavina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Attanasio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. P. O.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Pacini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Papini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Pierattelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. C.","family":"Felli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"issue":"1","key":"46442_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","volume":"23","author":"CB Jackson","year":"2022","unstructured":"Jackson, C. B., Farzan, M., Chen, B. & Choe, H. Mechanisms of SARS-CoV-2 Entry into Cells. Nat. Rev. Mol. Cell Biol. 23(1), 3\u201320. https:\/\/doi.org\/10.1038\/s41580-021-00418-x (2022).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"7","key":"46442_CR2","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/s41423-020-0374-2","volume":"17","author":"S Xia","year":"2020","unstructured":"Xia, S. et al. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell. Mol. Immunol. 17(7), 765\u2013767. https:\/\/doi.org\/10.1038\/s41423-020-0374-2 (2020).","journal-title":"Cell. Mol. Immunol."},{"issue":"11","key":"46442_CR3","doi-asserted-by":"publisher","first-page":"6647","DOI":"10.1093\/nar\/gkae256","volume":"52","author":"H Zhao","year":"2024","unstructured":"Zhao, H. et al. Assembly of SARS-CoV-2 nucleocapsid protein with nucleic acid. Nucleic Acids Res. 52(11), 6647\u20136661. https:\/\/doi.org\/10.1093\/nar\/gkae256 (2024).","journal-title":"Nucleic Acids Res."},{"key":"46442_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.129523","volume":"260","author":"A Eltayeb","year":"2024","unstructured":"Eltayeb, A. et al. Overview of the SARS-CoV-2 nucleocapsid protein. Int. J. Biol. Macromol. 260, 129523. https:\/\/doi.org\/10.1016\/j.ijbiomac.2024.129523 (2024).","journal-title":"Int. J. Biol. Macromol."},{"key":"46442_CR5","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.ijbiomac.2022.01.121","volume":"203","author":"IP Caruso","year":"2022","unstructured":"Caruso, I. P. et al. Insights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein n-terminal domain with deoxyribonucleic acids. Int. J. Biol. Macromol. 203, 466\u2013480. https:\/\/doi.org\/10.1016\/j.ijbiomac.2022.01.121 (2022).","journal-title":"Int. J. Biol. Macromol."},{"issue":"15","key":"46442_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167108","volume":"433","author":"JS Redzic","year":"2021","unstructured":"Redzic, J. S. et al. The inherent dynamics and interaction sites of the SARS-CoV-2 nucleocapsid N-terminal region. J. Mol. Biol. 433(15), 167108. https:\/\/doi.org\/10.1016\/j.jmb.2021.167108 (2021).","journal-title":"J. Mol. Biol."},{"issue":"1","key":"46442_CR7","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1038\/s41467-023-38882-y","volume":"14","author":"SM Korn","year":"2023","unstructured":"Korn, S. M., Dhamotharan, K., Jeffries, C. M. & Schlundt, A. The preference signature of the SARS-CoV-2 nucleocapsid NTD for its 5\u2019-genomic RNA elements. Nat. Commun. 14(1), 3331. https:\/\/doi.org\/10.1038\/s41467-023-38882-y (2023).","journal-title":"Nat. Commun."},{"issue":"12","key":"46442_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009100","volume":"16","author":"DC Dinesh","year":"2020","unstructured":"Dinesh, D. C. et al. Structural basis of RNA recognition by the SARS-CoV-2 nucleocapsid phosphoprotein. PLOS Pathog. 16(12), e1009100. https:\/\/doi.org\/10.1371\/journal.ppat.1009100 (2020).","journal-title":"PLOS Pathog."},{"issue":"6","key":"46442_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107354","volume":"300","author":"H Stuwe","year":"2024","unstructured":"Stuwe, H. et al. Phosphorylation in the Ser\/Arg-rich region of the nucleocapsid of SARS-CoV-2 regulates phase separation by inhibiting self-association of a distant helix. J. Biol. Chem. 300(6), 107354. https:\/\/doi.org\/10.1016\/j.jbc.2024.107354 (2024).","journal-title":"J. Biol. Chem."},{"issue":"7","key":"46442_CR10","doi-asserted-by":"publisher","first-page":"929","DOI":"10.3390\/biom12070929","volume":"12","author":"L Pontoriero","year":"2022","unstructured":"Pontoriero, L. et al. NMR reveals specific tracts within the intrinsically disordered regions of the SARS-CoV-2 nucleocapsid protein involved in RNA encountering. Biomolecules 12(7), 929. https:\/\/doi.org\/10.3390\/biom12070929 (2022).","journal-title":"Biomolecules"},{"issue":"1","key":"46442_CR11","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s12104-021-10009-8","volume":"15","author":"M Schiavina","year":"2021","unstructured":"Schiavina, M., Pontoriero, L., Uversky, V. N., Felli, I. C. & Pierattelli, R. The highly flexible disordered regions of the SARS-CoV-2 nucleocapsid N protein within the 1\u2013248 residue construct: Sequence-specific resonance assignments through NMR. Biomol. NMR. Assign. 15(1), 219\u2013227. https:\/\/doi.org\/10.1007\/s12104-021-10009-8 (2021).","journal-title":"Biomol. NMR. Assign."},{"issue":"10","key":"46442_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/pnasnexus\/pgad333","volume":"2","author":"AB Estelle","year":"2023","unstructured":"Estelle, A. B. et al. RNA structure and multiple weak interactions balance the interplay between RNA binding and phase separation of SARS-CoV-2 Nucleocapsid. PNAS Nexus 2(10), 1\u201315. https:\/\/doi.org\/10.1093\/pnasnexus\/pgad333 (2023).","journal-title":"PNAS Nexus"},{"key":"46442_CR13","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm4034","volume":"8","author":"LM Bessa","year":"2022","unstructured":"Bessa, L. M. et al. The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner Nsp3a. Sci. Adv. 8, 4034 (2022).","journal-title":"Sci. Adv."},{"issue":"14","key":"46442_CR14","doi-asserted-by":"publisher","first-page":"2890","DOI":"10.1016\/j.bpj.2021.03.023","volume":"120","author":"HM Forsythe","year":"2021","unstructured":"Forsythe, H. M. et al. Multivalent binding of the partially disordered SARS-CoV-2 Nucleocapsid Phosphoprotein dimer to RNA. Biophys. J. 120(14), 2890\u20132901. https:\/\/doi.org\/10.1016\/j.bpj.2021.03.023 (2021).","journal-title":"Biophys. J."},{"issue":"13","key":"46442_CR15","doi-asserted-by":"publisher","first-page":"6589","DOI":"10.1021\/cr400525m","volume":"114","author":"R Van Der Lee","year":"2014","unstructured":"Van Der Lee, R. et al. Classification of intrinsically disordered regions and proteins. Chem. Rev. 114(13), 6589\u20136631. https:\/\/doi.org\/10.1021\/cr400525m (2014).","journal-title":"Chem. Rev."},{"issue":"13","key":"46442_CR16","doi-asserted-by":"publisher","first-page":"6806","DOI":"10.1021\/cr4007329","volume":"114","author":"M Fuxreiter","year":"2014","unstructured":"Fuxreiter, M. et al. Disordered proteinaceous machines. Chem. Rev. 114(13), 6806\u20136843. https:\/\/doi.org\/10.1021\/cr4007329 (2014).","journal-title":"Chem. Rev."},{"issue":"13","key":"46442_CR17","doi-asserted-by":"publisher","first-page":"6561","DOI":"10.1021\/cr400514h","volume":"114","author":"J Habchi","year":"2014","unstructured":"Habchi, J., Tompa, P., Longhi, S. & Uversky, V. N. Introducing protein intrinsic disorder. Chem. Rev. 114(13), 6561\u20136588. https:\/\/doi.org\/10.1021\/cr400514h (2014).","journal-title":"Chem. Rev."},{"issue":"1","key":"46442_CR18","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1146\/annurev.biophys.37.032807.125924","volume":"37","author":"VN Uversky","year":"2008","unstructured":"Uversky, V. N., Oldfield, C. J. & Dunker, A. K. Intrinsically disordered proteins in human diseases: Introducing the D2 concept. Annu. Rev. Biophys. 37(1), 215\u2013246. https:\/\/doi.org\/10.1146\/annurev.biophys.37.032807.125924 (2008).","journal-title":"Annu. Rev. Biophys."},{"issue":"9","key":"46442_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/biom12091302","volume":"12","author":"M Schiavina","year":"2022","unstructured":"Schiavina, M., Pontoriero, L., Tagliaferro, G., Pierattelli, R. & Felli, I. C. The role of disordered regions in orchestrating the properties of multidomain proteins: The SARS-CoV-2 nucleocapsid protein and its interaction with enoxaparin. Biomolecules 12(9), 1302. https:\/\/doi.org\/10.3390\/biom12091302 (2022).","journal-title":"Biomolecules"},{"issue":"11","key":"46442_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202420134","volume":"137","author":"AS Tino","year":"2025","unstructured":"Tino, A. S. et al. Revealing the potential of a chimaera: A peptide-peptide nucleic acid molecule designed to interact with the SARS-CoV-2 Nucleocapsid Protein. Angew. Chem. 137(11), e202420134. https:\/\/doi.org\/10.1002\/ange.202420134 (2025).","journal-title":"Angew. Chem."},{"key":"46442_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2025.169437","author":"T Bolognesi","year":"2025","unstructured":"Bolognesi, T. et al. Exploring the role of structural and dynamic complexity in SARS-CoV-2 nucleocapsid protein\u2013heparin interactions by NMR. J. Mol. Biol. https:\/\/doi.org\/10.1016\/j.jmb.2025.169437 (2025).","journal-title":"J. Mol. Biol."},{"key":"46442_CR22","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax2323","volume":"10","author":"M Botova","year":"2024","unstructured":"Botova, M. et al. A specific phosphorylation-dependent conformational switch in SARS-CoV-2 nucleocapsid protein inhibits RNA binding. Sci. Adv. 10, 2323 (2024).","journal-title":"Sci. Adv."},{"issue":"8","key":"46442_CR23","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1074\/JBC.REV119.009847","volume":"295","author":"AC Murthy","year":"2020","unstructured":"Murthy, A. C. & Fawzi, N. L. The (un)structural biology of biomolecular liquid-liquid phase separation using NMR spectroscopy. J. Biol. Chem. 295(8), 2375\u20132384. https:\/\/doi.org\/10.1074\/JBC.REV119.009847 (2020).","journal-title":"J. Biol. Chem."},{"issue":"1","key":"46442_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19843-1","volume":"11","author":"A Savastano","year":"2020","unstructured":"Savastano, A., Opakua, AIde, Rankovic, M. & Zweckstetter, M. Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nat. Commun. 11(1), 6041. https:\/\/doi.org\/10.1038\/s41467-020-19843-1 (2020).","journal-title":"Nat. Commun."},{"issue":"5","key":"46442_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115512","volume":"44","author":"J Fahoum","year":"2025","unstructured":"Fahoum, J. et al. Transfer of SARS-CoV-2 Nucleocapsid Protein to uninfected epithelial cells induces antibody-mediated complement deposition. Cell Rep. 44(5), 115512. https:\/\/doi.org\/10.1016\/j.celrep.2025.115512 (2025).","journal-title":"Cell Rep."},{"issue":"17","key":"46442_CR26","doi-asserted-by":"publisher","first-page":"4328","DOI":"10.1002\/chem.201704307","volume":"24","author":"SL Grage","year":"2018","unstructured":"Grage, S. L. et al. Orthogonal 19F\u2010labeling for solid\u2010state nmr spectroscopy reveals the conformation and orientation of short peptaibols in membranes. Chem. A Eur. J. 24(17), 4328\u20134335. https:\/\/doi.org\/10.1002\/chem.201704307 (2018).","journal-title":"Chem. A Eur. J."},{"key":"46442_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnmrs.2025.101577","volume":"148\u2013149","author":"T Bolognesi","year":"2025","unstructured":"Bolognesi, T., Schiavina, M., Felli, I. C. & Pierattelli, R. NMR insights on multidomain proteins: The case of the SARS-CoV-2 nucleoprotein. Prog. Nucl. Magn. Reson. Spectrosc. 148\u2013149, 101577. https:\/\/doi.org\/10.1016\/j.pnmrs.2025.101577 (2025).","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"issue":"11","key":"46442_CR28","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1093\/bioinformatics\/bts172","volume":"28","author":"V Ozenne","year":"2012","unstructured":"Ozenne, V. et al. Flexible-Meccano: A tool for the generation of explicit ensemble descriptions of intrinsically disordered proteins and their associated experimental observables. Bioinformatics 28(11), 1463\u20131470. https:\/\/doi.org\/10.1093\/bioinformatics\/bts172 (2012).","journal-title":"Bioinformatics"},{"issue":"27\u201328","key":"46442_CR29","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1002\/ejoc.201800803","volume":"2018","author":"S Huhmann","year":"2018","unstructured":"Huhmann, S. & Koksch, B. Fine-tuning the proteolytic stability of peptides with fluorinated amino acids. Eur. J. Org. Chem. 2018(27\u201328), 3667\u20133679. https:\/\/doi.org\/10.1002\/ejoc.201800803 (2018).","journal-title":"Eur. J. Org. Chem."},{"issue":"6","key":"46442_CR30","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1039\/C1CS15241F","volume":"41","author":"M Salwiczek","year":"2012","unstructured":"Salwiczek, M., Nyakatura, E. K., Gerling, U. I. M., Ye, S. & Koksch, B. Fluorinated amino acids: Compatibility with native protein structures and effects on protein-protein interactions. Chem. Soc. Rev. 41(6), 2135\u20132171. https:\/\/doi.org\/10.1039\/C1CS15241F (2012).","journal-title":"Chem. Soc. Rev."},{"issue":"4","key":"46442_CR31","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.1021\/acssensors.5c00432","volume":"10","author":"H Qianzhu","year":"2025","unstructured":"Qianzhu, H., Tan, Y. J., Abdelkader, E. H., Huber, T. & Otting, G. Genetic encoding of fluorinated analogues of phenylalanine for 19F NMR spectroscopy: Detection of conformational heterogeneity in Flaviviral NS2B-NS3 proteases. ACS Sens. 10(4), 3152\u20133161. https:\/\/doi.org\/10.1021\/acssensors.5c00432 (2025).","journal-title":"ACS Sens."},{"issue":"12","key":"46442_CR32","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1093\/bioinformatics\/btx085","volume":"33","author":"D Piovesan","year":"2017","unstructured":"Piovesan, D., Walsh, I., Minervini, G. & Tosatto, S. C. E. FELLS: Fast estimator of latent local structure. Bioinformatics 33(12), 1889\u20131891. https:\/\/doi.org\/10.1093\/bioinformatics\/btx085 (2017).","journal-title":"Bioinformatics"},{"issue":"1","key":"46442_CR33","doi-asserted-by":"publisher","DOI":"10.1002\/psc.3457","volume":"29","author":"FM Paulussen","year":"2023","unstructured":"Paulussen, F. M. & Grossmann, T. N. Peptide\u2010based covalent inhibitors of protein\u2013protein interactions. J. Pept. Sci. 29(1), e3457. https:\/\/doi.org\/10.1002\/psc.3457 (2023).","journal-title":"J. Pept. Sci."},{"issue":"25","key":"46442_CR34","doi-asserted-by":"publisher","first-page":"22665","DOI":"10.1021\/acsomega.3c01436","volume":"8","author":"M Quagliata","year":"2023","unstructured":"Quagliata, M., Stincarelli, M. A., Papini, A. M., Giannecchini, S. & Rovero, P. Antiviral activity against SARS-CoV-2 of conformationally constrained helical peptides derived from angiotensin-converting enzyme 2. ACS Omega 8(25), 22665\u201322672. https:\/\/doi.org\/10.1021\/acsomega.3c01436 (2023).","journal-title":"ACS Omega"},{"issue":"11","key":"46442_CR35","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1021\/acs.jpcb.3c07511","volume":"128","author":"U Zavrtanik","year":"2024","unstructured":"Zavrtanik, U., Lah, J. & Had\u017ei, S. Estimation of peptide helicity from circular dichroism using the ensemble model. J. Phys. Chem. B 128(11), 2652\u20132663. https:\/\/doi.org\/10.1021\/acs.jpcb.3c07511 (2024).","journal-title":"J. Phys. Chem. B"},{"issue":"4","key":"46442_CR36","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1021\/jacs.3c11614","volume":"146","author":"GT Heller","year":"2024","unstructured":"Heller, G. T., Shukla, V. K., Figueiredo, A. M. & Hansen, D. F. Picosecond dynamics of a small molecule in its bound state with an intrinsically disordered protein. J. Am. Chem. Soc. 146(4), 2319\u20132324. https:\/\/doi.org\/10.1021\/jacs.3c11614 (2024).","journal-title":"J. Am. Chem. Soc."},{"issue":"2","key":"46442_CR37","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/mrc.4500","volume":"55","author":"C Dalvit","year":"2017","unstructured":"Dalvit, C. & Piotto, M. 19F NMR transverse and longitudinal relaxation filter experiments for screening: A theoretical and experimental analysis. Magn. Reson. Chem. 55(2), 106\u2013114. https:\/\/doi.org\/10.1002\/mrc.4500 (2017).","journal-title":"Magn. Reson. Chem."},{"issue":"12","key":"46442_CR38","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s10858-020-00348-4","volume":"74","author":"JH Overbeck","year":"2020","unstructured":"Overbeck, J. H., Kremer, W. & Sprangers, R. A suite of 19F based relaxation dispersion experiments to assess biomolecular motions. J. Biomol. NMR 74(12), 753\u2013766. https:\/\/doi.org\/10.1007\/s10858-020-00348-4 (2020).","journal-title":"J. Biomol. NMR"},{"issue":"8","key":"46442_CR39","doi-asserted-by":"publisher","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","volume":"61","author":"J Eberhardt","year":"2021","unstructured":"Eberhardt, J., Santos-Martins, D., Tillack, A. F. & Forli, S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model. 61(8), 3891\u20133898. https:\/\/doi.org\/10.1021\/acs.jcim.1c00203 (2021).","journal-title":"J. Chem. Inf. Model."},{"issue":"7","key":"46442_CR40","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1021\/ct400341p","volume":"9","author":"DR Roe","year":"2013","unstructured":"Roe, D. R. & Cheatham, T. E. PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data. J. Chem. Theory Comput. 9(7), 3084\u20133095. https:\/\/doi.org\/10.1021\/ct400341p (2013).","journal-title":"J. Chem. Theory Comput."},{"issue":"1","key":"46442_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03647-8","volume":"5","author":"JR Ciges-Tomas","year":"2022","unstructured":"Ciges-Tomas, J. R., Franco, M. L. & Vilar, M. Identification of a Guanine-specific pocket in the Protein N of SARS-CoV-2. Commun. Biol. 5(1), 711. https:\/\/doi.org\/10.1038\/s42003-022-03647-8 (2022).","journal-title":"Commun. Biol."},{"key":"46442_CR42","doi-asserted-by":"publisher","DOI":"10.1002\/psc.3605","author":"L Pacini","year":"2024","unstructured":"Pacini, L. et al. Optimization of peptide synthesis time and sustainability using novel eco\u2010friendly binary solvent systems with induction heating on an automated peptide synthesizer. J. Pept. Sci. https:\/\/doi.org\/10.1002\/psc.3605 (2024).","journal-title":"J. Pept. Sci."},{"key":"46442_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2020.108304","volume":"683","author":"F Munari","year":"2020","unstructured":"Munari, F., D\u2019Onofrio, M. & Assfalg, M. Solution NMR insights into dynamic supramolecular assemblies of disordered amyloidogenic proteins. Arch. Biochem. Biophys. 683, 108304. https:\/\/doi.org\/10.1016\/j.abb.2020.108304 (2020).","journal-title":"Arch. Biochem. Biophys."},{"issue":"31","key":"46442_CR44","doi-asserted-by":"publisher","first-page":"5167","DOI":"10.1021\/bi400502c","volume":"52","author":"D Kurzbach","year":"2013","unstructured":"Kurzbach, D. et al. Cooperative unfolding of compact conformations of the intrinsically disordered protein osteopontin. Biochemistry 52(31), 5167\u20135175. https:\/\/doi.org\/10.1021\/bi400502c (2013).","journal-title":"Biochemistry"},{"issue":"11","key":"46442_CR45","doi-asserted-by":"publisher","first-page":"6424","DOI":"10.1021\/acs.chemrev.5b00548","volume":"116","author":"V Csizmok","year":"2016","unstructured":"Csizmok, V., Follis, A. V., Kriwacki, R. W. & Forman-Kay, J. D. Dynamic protein interaction networks and new structural paradigms in signaling. Chem. Rev. 116(11), 6424\u20136462. https:\/\/doi.org\/10.1021\/acs.chemrev.5b00548 (2016).","journal-title":"Chem. Rev."},{"key":"46442_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2019.108161","volume":"677","author":"M Arbes\u00fa","year":"2019","unstructured":"Arbes\u00fa, M. & Pons, M. Integrating disorder in globular multidomain proteins: Fuzzy sensors and the role of SH3 domains. Arch. Biochem. Biophys. 677, 108161. https:\/\/doi.org\/10.1016\/j.abb.2019.108161 (2019).","journal-title":"Arch. Biochem. Biophys."},{"issue":"15","key":"46442_CR47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2425831122","volume":"122","author":"G Viola","year":"2025","unstructured":"Viola, G. et al. Conformational signatures induced by Ubiquitin modification in the amyloid-forming Tau repeat domain. Proc. Natl. Acad. Sci. 122(15), e2425831122. https:\/\/doi.org\/10.1073\/pnas.2425831122 (2025).","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"13","key":"46442_CR48","doi-asserted-by":"publisher","first-page":"6779","DOI":"10.1021\/cr400459c","volume":"114","author":"U Jakob","year":"2014","unstructured":"Jakob, U., Kriwacki, R. & Uversky, V. N. Conditionally and transiently disordered proteins: Awakening cryptic disorder to regulate protein function. Chem. Rev. 114(13), 6779\u20136805. https:\/\/doi.org\/10.1021\/cr400459c (2014).","journal-title":"Chem. Rev."},{"issue":"45","key":"46442_CR49","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb5924","volume":"6","author":"GT Heller","year":"2020","unstructured":"Heller, G. T. et al. Small-molecule sequestration of amyloid-\u03b2 as a drug discovery strategy for Alzheimer\u2019s disease. Sci. Adv. 6(45), eabb5924. https:\/\/doi.org\/10.1126\/sciadv.abb5924 (2020).","journal-title":"Sci. Adv."},{"issue":"33","key":"46442_CR50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2409167121","volume":"121","author":"M Watson","year":"2024","unstructured":"Watson, M. et al. A DNA condensation code for linker histones. Proc. Natl. Acad. Sci. 121(33), e2409167121. https:\/\/doi.org\/10.1073\/pnas.2409167121 (2024).","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"7694","key":"46442_CR51","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature25762","volume":"555","author":"A Borgia","year":"2018","unstructured":"Borgia, A. et al. Extreme disorder in an ultrahigh-affinity protein complex. Nature 555(7694), 61\u201366. https:\/\/doi.org\/10.1038\/nature25762 (2018).","journal-title":"Nature"},{"issue":"15","key":"46442_CR52","doi-asserted-by":"publisher","first-page":"3311","DOI":"10.1021\/acs.biochem.5c00101","volume":"64","author":"M Quagliata","year":"2025","unstructured":"Quagliata, M. et al. \u03b1-Helical structure of antimicrobial peptides enhances their activity through molecular surface signatures. Biochemistry 64(15), 3311\u20133321. https:\/\/doi.org\/10.1021\/acs.biochem.5c00101 (2025).","journal-title":"Biochemistry"},{"key":"46442_CR53","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.653148","author":"N Altincekic","year":"2021","unstructured":"Altincekic, N. et al. Large-scale recombinant production of the SARS-CoV-2 Proteome For High-Throughput And Structural Biology applications. Front. Mol. Biosci. https:\/\/doi.org\/10.3389\/fmolb.2021.653148 (2021).","journal-title":"Front. Mol. Biosci."},{"issue":"1","key":"46442_CR54","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/0022-2364(91)90036-S","volume":"93","author":"AG Palmer","year":"1991","unstructured":"Palmer, A. G., Cavanagh, J., Wright, P. E. & Rance, M. Sensitivity improvement in proton-detected two-dimensional heteronuclear correlation NMR spectroscopy. J. Magn. Reson. 93(1), 151\u2013170. https:\/\/doi.org\/10.1016\/0022-2364(91)90036-S (1991).","journal-title":"J. Magn. Reson."},{"issue":"2","key":"46442_CR55","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/BF00175254","volume":"4","author":"J Schleucher","year":"1994","unstructured":"Schleucher, J. et al. A general enhancement scheme in heteronuclear multidimensional NMR employing pulsed field gradients. J. Biomol. NMR. 4(2), 301\u2013306. https:\/\/doi.org\/10.1007\/BF00175254 (1994).","journal-title":"J. Biomol. NMR."},{"issue":"5","key":"46442_CR56","doi-asserted-by":"publisher","first-page":"2218","DOI":"10.1021\/acs.jmedchem.8b01210","volume":"62","author":"C Dalvit","year":"2019","unstructured":"Dalvit, C. & Vulpetti, A. Ligand-based fluorine NMR screening: Principles and applications in drug discovery projects. J. Med. Chem. 62(5), 2218\u20132244. https:\/\/doi.org\/10.1021\/acs.jmedchem.8b01210 (2019).","journal-title":"J. Med. Chem."},{"issue":"1","key":"46442_CR57","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.str.2021.09.009","volume":"30","author":"AM Gronenborn","year":"2022","unstructured":"Gronenborn, A. M. Small, but powerful and attractive: 19F in biomolecular NMR. Structure 30(1), 6\u201314. https:\/\/doi.org\/10.1016\/j.str.2021.09.009 (2022).","journal-title":"Structure"},{"key":"46442_CR58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/J.PNMRS.2013.02.001","volume":"73","author":"MP Williamson","year":"2013","unstructured":"Williamson, M. P. Using chemical shift perturbation to characterise ligand binding. Prog. Nucl. Magn. Reson. Spectrosc. 73, 1\u201316. https:\/\/doi.org\/10.1016\/J.PNMRS.2013.02.001 (2013).","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"issue":"2","key":"46442_CR59","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31(2), 455\u2013461. https:\/\/doi.org\/10.1002\/jcc.21334 (2010).","journal-title":"J. Comput. Chem."},{"issue":"16","key":"46442_CR60","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","volume":"26","author":"D Van Der Spoel","year":"2005","unstructured":"Van Der Spoel, D. et al. GROMACS: Fast, flexible, and free. J. Comput. Chem. 26(16), 1701\u20131718. https:\/\/doi.org\/10.1002\/jcc.20291 (2005).","journal-title":"J. Comput. Chem."},{"issue":"8","key":"46442_CR61","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1016\/j.bpj.2017.03.011","volume":"112","author":"MW Maciejewski","year":"2017","unstructured":"Maciejewski, M. W. et al. NMRbox: A resource for biomolecular NMR computation. Biophys. J. 112(8), 1529\u20131534. https:\/\/doi.org\/10.1016\/j.bpj.2017.03.011 (2017).","journal-title":"Biophys. J."},{"issue":"16","key":"46442_CR62","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris, G. M. et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 30(16), 2785\u20132791. https:\/\/doi.org\/10.1002\/jcc.21256 (2009).","journal-title":"J. Comput. Chem."},{"issue":"20","key":"46442_CR63","doi-asserted-by":"publisher","first-page":"6183","DOI":"10.1021\/acs.jcim.3c01153","volume":"63","author":"DA Case","year":"2023","unstructured":"Case, D. A. et al. AmberTools. J. Chem. Inf. Model. 63(20), 6183\u20136191. https:\/\/doi.org\/10.1021\/acs.jcim.3c01153 (2023).","journal-title":"J. Chem. Inf. Model."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46442-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46442-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46442-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T22:46:58Z","timestamp":1781131618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46442-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,18]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["46442"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-46442-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,18]]},"assertion":[{"value":"12 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18060"}}