{"id":"https://openalex.org/W7206218142","doi":"https://doi.org/10.5281/zenodo.22258664","title":"Local Frustration Modulates the Folding Dynamics of a Repeat Protein","display_name":"Local Frustration Modulates the Folding Dynamics of a Repeat Protein","publication_year":2026,"publication_date":"2026-09-02","ids":{"openalex":"https://openalex.org/W7206218142","doi":"https://doi.org/10.5281/zenodo.22258664"},"language":"en","primary_location":{"id":"doi:10.5281/zenodo.22258664","doi":"https://doi.org/10.5281/zenodo.22258664","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.22258664","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Dataset"},"volume":null,"type":"dataset","indexed_in":["datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.5281/zenodo.22258664","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5065236542","display_name":"Murilo N. Sanches","orcid":"https://orcid.org/0000-0001-9650-7989","observed_orcids":["https://orcid.org/0000-0001-9650-7989"]},"institutions":[{"id":"https://openalex.org/I879563668","display_name":"Universidade Estadual Paulista (Unesp)","ror":"https://ror.org/00987cb86","country_code":"BR","type":"education","lineage":["https://openalex.org/I879563668"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Nogueira Sanches, Murilo","raw_affiliation_strings":["Universidade Estadual Paulista (Unesp)"],"raw_orcid":"https://orcid.org/0000-0001-9650-7989","affiliations":[{"raw_affiliation_string":"Universidade Estadual Paulista (Unesp)","institution_ids":["https://openalex.org/I879563668"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081738012","display_name":"Mar\u00eda In\u00e9s Freiberger","orcid":"https://orcid.org/0000-0002-5634-1897","observed_orcids":["https://orcid.org/0000-0002-5634-1897"]},"institutions":[{"id":"https://openalex.org/I39804081","display_name":"Sorbonne Universit\u00e9","ror":"https://ror.org/02en5vm52","country_code":"FR","type":"education","lineage":["https://openalex.org/I39804081"]}],"countries":["FR"],"is_corresponding":false,"raw_author_name":"Ines Freiberger, Maria","raw_affiliation_strings":["Sorbonne Universit\u00e9"],"raw_orcid":"https://orcid.org/0000-0002-5634-1897","affiliations":[{"raw_affiliation_string":"Sorbonne Universit\u00e9","institution_ids":["https://openalex.org/I39804081"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023161837","display_name":"Peter Guy Wolynes","orcid":"https://orcid.org/0000-0001-7975-9287","observed_orcids":["https://orcid.org/0000-0001-7975-9287"]},"institutions":[{"id":"https://openalex.org/I74775410","display_name":"Rice University","ror":"https://ror.org/008zs3103","country_code":"US","type":"education","lineage":["https://openalex.org/I74775410"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wolynes, Peter","raw_affiliation_strings":["Rice University"],"raw_orcid":"https://orcid.org/0000-0001-7975-9287","affiliations":[{"raw_affiliation_string":"Rice University","institution_ids":["https://openalex.org/I74775410"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026249041","display_name":"Diego Ulises Ferreiro","orcid":"https://orcid.org/0000-0002-7869-4247","observed_orcids":["https://orcid.org/0000-0002-7869-4247"]},"institutions":[{"id":"https://openalex.org/I24354313","display_name":"Universidad de Buenos Aires","ror":"https://ror.org/0081fs513","country_code":"AR","type":"education","lineage":["https://openalex.org/I24354313"]}],"countries":["AR"],"is_corresponding":false,"raw_author_name":"Ferreiro, Diego","raw_affiliation_strings":["Universidad de Buenos Aires"],"raw_orcid":"https://orcid.org/0000-0002-7869-4247","affiliations":[{"raw_affiliation_string":"Universidad de Buenos Aires","institution_ids":["https://openalex.org/I24354313"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5024994552","display_name":"Vitor B. P. Leite","orcid":"https://orcid.org/0000-0003-0008-9079","observed_orcids":["https://orcid.org/0000-0003-0008-9079"]},"institutions":[{"id":"https://openalex.org/I879563668","display_name":"Universidade Estadual Paulista (Unesp)","ror":"https://ror.org/00987cb86","country_code":"BR","type":"education","lineage":["https://openalex.org/I879563668"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Barbanti Pereira Leite, Vitor","raw_affiliation_strings":["Universidade Estadual Paulista (Unesp)"],"raw_orcid":"https://orcid.org/0000-0003-0008-9079","affiliations":[{"raw_affiliation_string":"Universidade Estadual Paulista (Unesp)","institution_ids":["https://openalex.org/I879563668"]}]}],"institutions":[],"countries_distinct_count":4,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11124","display_name":"Protein purification and stability","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ankyrin-repeat-domain","display_name":"ankyrin repeat domain","score":0.7710000276565552},{"id":"https://openalex.org/keywords/ikappabalpha","display_name":"I\u03baB\u03b1","score":0.9990000128746033},{"id":"https://openalex.org/keywords/repeat-proteins","display_name":"repeat proteins","score":0.7870000004768372},{"id":"https://openalex.org/keywords/protein-folding-dynamics","display_name":"protein folding dynamics","score":0.8700000047683716},{"id":"https://openalex.org/keywords/folding-intermediates","display_name":"folding intermediates","score":0.7080000042915344},{"id":"https://openalex.org/keywords/kinetic-trapping","display_name":"kinetic trapping","score":0.8519999980926514},{"id":"https://openalex.org/keywords/folding-funnel","display_name":"folding funnel","score":0.5730000138282776},{"id":"https://openalex.org/keywords/genetic-variants","display_name":"genetic variants","score":0.40799999237060547},{"id":"https://openalex.org/keywords/energy-landscape","display_name":"energy landscape","score":0.5099999904632568}],"concepts":[{"id":"https://openalex.org/C204328495","wikidata":"https://www.wikidata.org/wiki/Q847556","display_name":"Protein folding","level":2,"score":0.6941999793052673},{"id":"https://openalex.org/C119621388","wikidata":"https://www.wikidata.org/wiki/Q5377166","display_name":"Energy landscape","level":2,"score":0.6715999841690063},{"id":"https://openalex.org/C2776545253","wikidata":"https://www.wikidata.org/wiki/Q5464292","display_name":"Folding (DSP implementation)","level":2,"score":0.6261000037193298},{"id":"https://openalex.org/C206276672","wikidata":"https://www.wikidata.org/wiki/Q5164839","display_name":"Contact order","level":3,"score":0.46700000762939453},{"id":"https://openalex.org/C38710091","wikidata":"https://www.wikidata.org/wiki/Q192242","display_name":"Frustration","level":2,"score":0.45969998836517334},{"id":"https://openalex.org/C46449900","wikidata":"https://www.wikidata.org/wiki/Q5303170","display_name":"Downhill folding","level":4,"score":0.4343000054359436},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.43309998512268066},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.4244000017642975},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.38960000872612},{"id":"https://openalex.org/C174507519","wikidata":"https://www.wikidata.org/wiki/Q5464306","display_name":"Folding funnel","level":5,"score":0.382999986410141},{"id":"https://openalex.org/C113241181","wikidata":"https://www.wikidata.org/wiki/Q24784174","display_name":"Ankyrin repeat","level":3,"score":0.36809998750686646},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.35530000925064087},{"id":"https://openalex.org/C2781085045","wikidata":"https://www.wikidata.org/wiki/Q7318308","display_name":"Reversing","level":2,"score":0.3447999954223633},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3361999988555908},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.3294999897480011},{"id":"https://openalex.org/C144292202","wikidata":"https://www.wikidata.org/wiki/Q898273","display_name":"Protein domain","level":3,"score":0.32519999146461487},{"id":"https://openalex.org/C145912823","wikidata":"https://www.wikidata.org/wiki/Q113558","display_name":"Dynamics (music)","level":2,"score":0.321399986743927},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.31929999589920044},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.31690001487731934},{"id":"https://openalex.org/C19472624","wikidata":"https://www.wikidata.org/wiki/Q583851","display_name":"Native state","level":2,"score":0.3158999979496002},{"id":"https://openalex.org/C32598905","wikidata":"https://www.wikidata.org/wiki/Q6497130","display_name":"Lattice protein","level":3,"score":0.3093999922275543},{"id":"https://openalex.org/C101468663","wikidata":"https://www.wikidata.org/wiki/Q1620158","display_name":"Modular design","level":2,"score":0.3003000020980835},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.2973000109195709},{"id":"https://openalex.org/C36503486","wikidata":"https://www.wikidata.org/wiki/Q11235244","display_name":"Domain (mathematical analysis)","level":2,"score":0.2906000018119812},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.28690001368522644},{"id":"https://openalex.org/C53942344","wikidata":"https://www.wikidata.org/wiki/Q951651","display_name":"Fold (higher-order function)","level":2,"score":0.26989999413490295},{"id":"https://openalex.org/C182800266","wikidata":"https://www.wikidata.org/wiki/Q414971","display_name":"Ankyrin","level":3,"score":0.26930001378059387},{"id":"https://openalex.org/C149774189","wikidata":"https://www.wikidata.org/wiki/Q24770541","display_name":"Immunoglobulin domain","level":3,"score":0.2671000063419342},{"id":"https://openalex.org/C135889238","wikidata":"https://www.wikidata.org/wiki/Q46276","display_name":"Kinetic energy","level":2,"score":0.26600000262260437},{"id":"https://openalex.org/C152769699","wikidata":"https://www.wikidata.org/wiki/Q410814","display_name":"Protein design","level":3,"score":0.2630999982357025},{"id":"https://openalex.org/C162203774","wikidata":"https://www.wikidata.org/wiki/Q7181581","display_name":"Phi value analysis","level":3,"score":0.25999999046325684},{"id":"https://openalex.org/C2986090443","wikidata":"https://www.wikidata.org/wiki/Q77870413","display_name":"Local structure","level":2,"score":0.2549999952316284}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.5281/zenodo.22258664","doi":"https://doi.org/10.5281/zenodo.22258664","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.22258664","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Dataset"},{"id":"doi:10.5281/zenodo.22258665","doi":"https://doi.org/10.5281/zenodo.22258665","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.22258665","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Dataset"}],"best_oa_location":{"id":"doi:10.5281/zenodo.22258664","doi":"https://doi.org/10.5281/zenodo.22258664","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.22258664","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Dataset"},"sustainable_development_goals":[],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2128925969","https://openalex.org/W2126189887","https://openalex.org/W2030100088","https://openalex.org/W2914214165","https://openalex.org/W7044152717","https://openalex.org/W2127023173","https://openalex.org/W2070582998","https://openalex.org/W2149243426","https://openalex.org/W2069633979","https://openalex.org/W2033619224"],"abstract_inverted_index":{"Repeat":[0],"proteins":[1],"fold":[2],"through":[3],"pathways":[4,67],"that":[5,114,168],"are":[6,37,43],"strongly":[7],"shaped":[8],"by":[9,138],"local":[10,81],"energetics,":[11],"making":[12],"them":[13],"highly":[14],"sensitive":[15],"to":[16,154,165],"mutations.":[17],"The":[18],"ankyrin":[19],"repeat":[20,198],"(AR)":[21],"domain":[22],"of":[23,106],"I\u03baB\u03b1":[24,50],"is":[25],"a":[26,52,119],"cooperative":[27],"folding":[28,54,66,105,121,195],"unit":[29],"in":[30,109,197],"which":[31,95,100],"the":[32,40,74,86,107,129,136,148,152,156,163],"first":[33],"four":[34],"repeats":[35],"(AR1\u2013AR4)":[36],"stable,":[38],"while":[39],"last":[41],"two":[42,91],"destabilized.":[44],"Despite":[45],"this":[46],"simple":[47],"modular":[48],"architecture,":[49],"follows":[51],"complex":[53],"trajectory":[55],"involving":[56],"high-energy":[57],"intermediates.":[58],"Here,":[59],"we":[60],"investigate":[61],"how":[62,183],"sequence":[63,185],"variations":[64],"modulate":[65,190],"using":[68],"coarse-grained":[69],"AWSEM":[70],"simulations":[71],"combined":[72],"with":[73,90,143],"Energy":[75],"Landscape":[76],"Visualization":[77],"Method":[78],"(ELViM)":[79],"and":[80,98,102,116,193],"frustration":[82],"analysis.":[83],"We":[84],"compare":[85],"wild":[87],"type":[88],"(WT)":[89],"consensus-designed":[92],"variants:":[93],"V93L,":[94],"accelerates":[96],"folding,":[97],"L131V,":[99],"destabilizes":[101],"slows":[103],"down":[104],"protein":[108,153,164],"vitro.":[110],"Our":[111],"results":[112],"show":[113],"WT":[115],"V93L":[117,124],"share":[118],"similar":[120],"funnel,":[122],"though":[123],"folds":[125],"more":[126],"directly":[127],"into":[128],"native":[130,157],"state.":[131],"In":[132],"contrast,":[133],"L131V":[134,149],"reshapes":[135],"landscape":[137],"stabilizing":[139],"non-native":[140],"kinetic":[141,191],"trap":[142],"minimally":[144],"frustrated":[145],"contacts.":[146],"Reversing":[147],"mutation":[150],"allows":[151],"reach":[155],"conformation,":[158],"whereas":[159],"maintaining":[160],"it":[161],"confines":[162],"misfolded":[166],"states":[167],"can":[169,187],"only":[170],"be":[171],"escaped":[172],"at":[173],"very":[174],"high":[175],"temperatures,":[176],"without":[177],"productive":[178],"folding.":[179],"These":[180],"findings":[181],"highlight":[182],"subtle":[184],"changes":[186],"tune":[188],"frustration,":[189],"trapping,":[192],"control":[194],"efficiency":[196],"proteins.":[199]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-09-03T00:00:00"}