{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:42:53Z","timestamp":1776318173209,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"W1","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"AIRC","doi-asserted-by":"publisher","award":["IG 26229"],"award-info":[{"award-number":["IG 26229"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Many proteins perform their functions within membraneless organelles, where they form a liquid-like condensed state, also known as droplet state. The FuzDrop method predicts the probability of spontaneous liquid\u2013liquid phase separation of proteins and provides a sequence-based score to identify the regions that promote this process. Furthermore, the FuzDrop method estimates the propensity of conversion of proteins to the amyloid state, and identifies aggregation hot-spots, which can drive the irreversible maturation of the liquid-like droplet state. These predictions can also identify mutations that can induce formation of amyloid aggregates, including those implicated in human diseases. To facilitate the interpretation of the predictions, the droplet-promoting and aggregation-promoting regions can be visualized on protein structures generated by AlphaFold. The FuzDrop server (https:\/\/fuzdrop.bio.unipd.it) thus offers insights into the complex behavior of proteins in their condensed states and facilitates the understanding of the functional relationships of proteins.<\/jats:p>","DOI":"10.1093\/nar\/gkac386","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T01:37:04Z","timestamp":1653442624000},"page":"W337-W344","source":"Crossref","is-referenced-by-count":141,"title":["FuzDrop on AlphaFold: visualizing the sequence-dependent propensity of liquid\u2013liquid phase separation and aggregation of proteins"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9224-9820","authenticated-orcid":false,"given":"Andras","family":"Hatos","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova , via Ugo Bassi 58\/B, 35131 Padova , Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-7793","authenticated-orcid":false,"given":"Silvio C E","family":"Tosatto","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova , via Ugo Bassi 58\/B, 35131 Padova , Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-1610","authenticated-orcid":false,"given":"Michele","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-6727","authenticated-orcid":false,"given":"Monika","family":"Fuxreiter","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova , via Ugo Bassi 58\/B, 35131 Padova , Italy"}]}],"member":"286","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"2022070500013972800_B1","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1126\/science.1172046","article-title":"Germline p granules are liquid droplets that localize by controlled dissolution\/condensation","volume":"324","author":"Brangwynne","year":"2009","journal-title":"Science"},{"key":"2022070500013972800_B2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrm.2017.7","article-title":"Biomolecular condensates: organizers of cellular biochemistry","volume":"18","author":"Banani","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022070500013972800_B3","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/j.cell.2018.10.042","article-title":"Transcription factors activate genes through the phase-separation capacity of their activation domains","volume":"175","author":"Boija","year":"2018","journal-title":"Cell"},{"key":"2022070500013972800_B4","doi-asserted-by":"crossref","first-page":"33254","DOI":"10.1073\/pnas.2007670117","article-title":"Widespread occurrence of the droplet state of proteins in the human proteome","volume":"117","author":"Hardenberg","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2022070500013972800_B5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-cellbio-100913-013325","article-title":"Liquid-liquid phase separation in biology","volume":"30","author":"Hyman","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2022070500013972800_B6","first-page":"235","article-title":"A framework for understanding the functions of biomolecular condensates across scales","volume":"21","author":"Lyon","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022070500013972800_B7","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41556-021-00697-8","article-title":"Generic nature of the condensed states of proteins","volume":"23","author":"Fuxreiter","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"2022070500013972800_B8","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1126\/science.aat1022","article-title":"DNA-induced liquid phase condensation of cGAS activates innate immune signaling","volume":"361","author":"Du","year":"2018","journal-title":"Science"},{"key":"2022070500013972800_B9","doi-asserted-by":"crossref","first-page":"e04123","DOI":"10.7554\/eLife.04123","article-title":"Phase transitions of multivalent proteins can promote clustering of membrane receptors","volume":"3","author":"Banjade","year":"2014","journal-title":"Elife"},{"key":"2022070500013972800_B10","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.devcel.2019.01.025","article-title":"Wnt\/Beta-Catenin signaling regulation and a role for biomolecular condensates","volume":"48","author":"Schaefer","year":"2019","journal-title":"Dev. Cell"},{"key":"2022070500013972800_B11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2017.05.028","article-title":"The centrosome is a selective condensate that nucleates microtubules by concentrating tubulin","volume":"169","author":"Woodruff","year":"2017","journal-title":"Cell"},{"key":"2022070500013972800_B12","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1126\/science.aau6313","article-title":"Stoichiometry controls activity of phase-separated clusters of actin signaling proteins","volume":"363","author":"Case","year":"2019","journal-title":"Science"},{"key":"2022070500013972800_B13","doi-asserted-by":"crossref","first-page":"e101379","DOI":"10.15252\/embj.2018101379","article-title":"Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments","volume":"38","author":"Kilic","year":"2019","journal-title":"EMBO J."},{"key":"2022070500013972800_B14","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature22822","article-title":"Liquid droplet formation by HP1alpha suggests a role for phase separation in heterochromatin","volume":"547","author":"Larson","year":"2017","journal-title":"Nature"},{"key":"2022070500013972800_B15","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2015.12.038","article-title":"ATPase-modulated stress granules contain a diverse proteome and substructure","volume":"164","author":"Jain","year":"2016","journal-title":"Cell"},{"key":"2022070500013972800_B16","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.molcel.2019.09.014","article-title":"Properties of stress granule and P-Body proteomes","volume":"76","author":"Youn","year":"2019","journal-title":"Mol. Cell"},{"key":"2022070500013972800_B17","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41580-020-00326-6","article-title":"Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing","volume":"22","author":"Alberti","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022070500013972800_B18","first-page":"282","article-title":"Observation of an alpha-synuclein liquid droplet state and its maturation into lewy body-like assemblies","volume":"13","author":"Hardenberg","year":"2021","journal-title":"J. Mol. Cell Biol."},{"key":"2022070500013972800_B19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature11922","article-title":"Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS","volume":"495","author":"Kim","year":"2013","journal-title":"Nature"},{"key":"2022070500013972800_B20","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.abb8032","article-title":"Beyond aggregation: pathological phase transitions in neurodegenerative disease","volume":"370","author":"Mathieu","year":"2020","journal-title":"Science"},{"key":"2022070500013972800_B21","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ccell.2020.12.003","article-title":"Biomolecular condensates and cancer","volume":"39","author":"Boija","year":"2021","journal-title":"Cancer Cell"},{"key":"2022070500013972800_B22","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/s41586-021-03703-z","article-title":"A condensate-hardening drug blocks RSV replication in vivo","volume":"595","author":"Risso-Ballester","year":"2021","journal-title":"Nature"},{"key":"2022070500013972800_B23","doi-asserted-by":"crossref","first-page":"167201","DOI":"10.1016\/j.jmb.2021.167201","article-title":"Sequence determinants of the aggregation of proteins within condensates generated by liquid\u2013liquid phase separation","volume":"434","author":"Vendruscolo","year":"2021","journal-title":"J. Mol. Biol."},{"key":"2022070500013972800_B24","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1016\/j.jmb.2020.02.017","article-title":"Sequence-Based prediction of fuzzy protein interactions","volume":"432","author":"Miskei","year":"2020","journal-title":"J. Mol. Biol."},{"key":"2022070500013972800_B25","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.tibs.2007.10.003","article-title":"Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions","volume":"33","author":"Tompa","year":"2008","journal-title":"Trends Biochem. Sci"},{"key":"2022070500013972800_B26","doi-asserted-by":"crossref","first-page":"8615","DOI":"10.3390\/ijms21228615","article-title":"Classifying the binding modes of disordered proteins","volume":"21","author":"Fuxreiter","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2022070500013972800_B27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.molcel.2015.08.018","article-title":"Formation and maturation of phase-separated liquid droplets by RNA-Binding proteins","volume":"60","author":"Lin","year":"2015","journal-title":"Mol. Cell"},{"key":"2022070500013972800_B28","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.1073\/pnas.84.20.7079","article-title":"Binary liquid phase separation and critical phenomena in a protein\/water solution","volume":"84","author":"Thomson","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2022070500013972800_B29","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.bpj.2020.08.002","article-title":"Phosphofructokinase relocalizes into subcellular compartments with liquid-like properties in vivo","volume":"120","author":"Jang","year":"2021","journal-title":"Biophys. J."},{"key":"2022070500013972800_B30","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1021\/acs.jpcb.0c11068","article-title":"Frustration in fuzzy protein complexes leads to interaction versatility","volume":"125","author":"Freiberger","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"2022070500013972800_B31","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1021\/acs.accounts.0c00813","article-title":"Fuzziness and frustration in the energy landscape of protein folding, function, and assembly","volume":"54","author":"Gianni","year":"2021","journal-title":"Acc. Chem. Res."},{"key":"2022070500013972800_B32","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/bioinformatics\/btr682","article-title":"ESpritz: accurate and fast prediction of protein disorder","volume":"28","author":"Walsh","year":"2012","journal-title":"Bioinformatics"},{"key":"2022070500013972800_B33","first-page":"D360","article-title":"PhaSePro: the database of proteins driving liquid\u2013liquid phase separation","volume":"48","author":"Meszaros","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B34","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nrm3810","article-title":"The amyloid state and its association with protein misfolding diseases","volume":"15","author":"Knowles","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022070500013972800_B35","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1002\/1873-3468.12762","article-title":"Fuzziness enables context dependence of protein interactions","volume":"591","author":"Miskei","year":"2017","journal-title":"FEBS Lett."},{"key":"2022070500013972800_B36","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1042\/BST20200239","article-title":"Fuzzy protein theory for disordered proteins","volume":"48","author":"Fuxreiter","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"2022070500013972800_B37","doi-asserted-by":"crossref","first-page":"e1007864","DOI":"10.1371\/journal.pcbi.1007864","article-title":"Sequence-based prediction of protein binding mode landscapes","volume":"16","author":"Horvath","year":"2020","journal-title":"PLoS Comp Biol"},{"key":"2022070500013972800_B38","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.molcel.2020.10.014","article-title":"ALS\/FTLD-Linked mutations in FUS glycine residues cause accelerated gelation and reduced interactions with wild-type FUS","volume":"80","author":"Rhine","year":"2020","journal-title":"Mol. Cell"},{"key":"2022070500013972800_B39","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: the universal protein knowledgebase in 2021","volume":"49","author":"UniProt","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B40","doi-asserted-by":"crossref","first-page":"D509","DOI":"10.1093\/nar\/gkab1060","article-title":"FuzDB: a new phase in understanding fuzzy interactions","volume":"50","author":"Hatos","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B41","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.cell.2013.01.033","article-title":"Dual specificity kinase DYRK3 couples stress granule condensation\/dissolution to mTORC1 signaling","volume":"152","author":"Wippich","year":"2013","journal-title":"Cell"},{"key":"2022070500013972800_B42","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","article-title":"Pfam: the protein families database in 2021","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B43","doi-asserted-by":"crossref","first-page":"D354","DOI":"10.1093\/nar\/gkz847","article-title":"PhaSepDB: a database of liquid\u2013liquid phase separation related proteins","volume":"48","author":"You","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B44","doi-asserted-by":"crossref","first-page":"D320","DOI":"10.1093\/nar\/gkz778","article-title":"LLPSDB: a database of proteins undergoing liquid\u2013liquid phase separation in vitro","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B45","first-page":"D269","article-title":"DisProt: intrinsic protein disorder annotation in 2020","volume":"48","author":"Hatos","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B46","doi-asserted-by":"crossref","first-page":"D404","DOI":"10.1093\/nar\/gkaa1021","article-title":"PED in 2021: a major update of the protein ensemble database for intrinsically disordered proteins","volume":"49","author":"Lazar","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B47","doi-asserted-by":"crossref","first-page":"W431","DOI":"10.1093\/nar\/gkab314","article-title":"Mol* viewer: modern web app for 3D visualization and analysis of large biomolecular structures","volume":"49","author":"Sehnal","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022070500013972800_B48","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with alphafold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2022070500013972800_B49","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/W1\/W337\/44379657\/gkac386.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/W1\/W337\/44379657\/gkac386.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:07:20Z","timestamp":1656979640000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/50\/W1\/W337\/6591523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":49,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2022,5,24]]},"published-print":{"date-parts":[[2022,7,5]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkac386","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,5]]},"published":{"date-parts":[[2022,5,24]]}}}