{"id":"https://openalex.org/W3201091795","doi":"https://doi.org/10.1021/acs.jcim.1c00712","title":"Accurate Binding Configuration Prediction of a G-Protein-Coupled Receptor to Its Antagonist Using Multicanonical Molecular Dynamics-Based Dynamic Docking","display_name":"Accurate Binding Configuration Prediction of a G-Protein-Coupled Receptor to Its Antagonist Using Multicanonical Molecular Dynamics-Based Dynamic Docking","publication_year":2021,"publication_date":"2021-09-22","ids":{"openalex":"https://openalex.org/W3201091795","doi":"https://doi.org/10.1021/acs.jcim.1c00712","mag":"3201091795","pmid":"https://pubmed.ncbi.nlm.nih.gov/34549581"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.1c00712","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.1c00712","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5058425101","display_name":"Gert\u2010Jan Bekker","orcid":"https://orcid.org/0000-0001-8385-5693"},"institutions":[{"id":"https://openalex.org/I98285908","display_name":"The University of Osaka","ror":"https://ror.org/035t8zc32","country_code":"JP","type":"education","lineage":["https://openalex.org/I98285908"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Gert-Jan Bekker","raw_affiliation_strings":["Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan"],"raw_orcid":"https://orcid.org/0000-0001-8385-5693","affiliations":[{"raw_affiliation_string":"Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan","institution_ids":["https://openalex.org/I98285908"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023816779","display_name":"Mitsugu Araki","orcid":"https://orcid.org/0000-0002-7810-4905"},"institutions":[{"id":"https://openalex.org/I22299242","display_name":"Kyoto University","ror":"https://ror.org/02kpeqv85","country_code":"JP","type":"education","lineage":["https://openalex.org/I22299242"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Mitsugu Araki","raw_affiliation_strings":["Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan"],"raw_orcid":"https://orcid.org/0000-0002-7810-4905","affiliations":[{"raw_affiliation_string":"Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan","institution_ids":["https://openalex.org/I22299242"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111840402","display_name":"Kanji Oshima","orcid":null},"institutions":[{"id":"https://openalex.org/I4210091817","display_name":"Takasago (Japan)","ror":"https://ror.org/00cty0112","country_code":"JP","type":"company","lineage":["https://openalex.org/I4210091817"]},{"id":"https://openalex.org/I4210131637","display_name":"Kaneka (Japan)","ror":"https://ror.org/038ckz871","country_code":"JP","type":"company","lineage":["https://openalex.org/I4210131637"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kanji Oshima","raw_affiliation_strings":["Biotechnology Research Laboratories, Kaneka Corporation, 1-8 Miyamae-cho, Takasago-cho, Takasago, Hyogo 676-8688, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biotechnology Research Laboratories, Kaneka Corporation, 1-8 Miyamae-cho, Takasago-cho, Takasago, Hyogo 676-8688, Japan","institution_ids":["https://openalex.org/I4210091817","https://openalex.org/I4210131637"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046211758","display_name":"Yasushi Okuno","orcid":"https://orcid.org/0000-0003-3596-4208"},"institutions":[{"id":"https://openalex.org/I22299242","display_name":"Kyoto University","ror":"https://ror.org/02kpeqv85","country_code":"JP","type":"education","lineage":["https://openalex.org/I22299242"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yasushi Okuno","raw_affiliation_strings":["Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan","institution_ids":["https://openalex.org/I22299242"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5065783054","display_name":"Narutoshi Kamiya","orcid":"https://orcid.org/0000-0002-0527-6968"},"institutions":[{"id":"https://openalex.org/I180941496","display_name":"University of Hyogo","ror":"https://ror.org/0151bmh98","country_code":"JP","type":"education","lineage":["https://openalex.org/I180941496"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Narutoshi Kamiya","raw_affiliation_strings":["Graduate School of Information Science, University of Hyogo, 7-1-28 Minatojima Minami-machi, Chuo-ku, Kobe, Hyogo 650-0047, Japan"],"raw_orcid":"https://orcid.org/0000-0002-0527-6968","affiliations":[{"raw_affiliation_string":"Graduate School of Information Science, University of Hyogo, 7-1-28 Minatojima Minami-machi, Chuo-ku, Kobe, Hyogo 650-0047, Japan","institution_ids":["https://openalex.org/I180941496"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5058425101","https://openalex.org/A5065783054"],"corresponding_institution_ids":["https://openalex.org/I180941496","https://openalex.org/I98285908"],"apc_list":null,"apc_paid":null,"fwci":1.1388,"has_fulltext":false,"cited_by_count":18,"citation_normalized_percentile":{"value":0.77784585,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"61","issue":"10","first_page":"5161","last_page":"5171"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9998999834060669,"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/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9998999834060669,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.9991000294685364,"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/T10683","display_name":"Mass Spectrometry Techniques and Applications","score":0.9980999827384949,"subfield":{"id":"https://openalex.org/subfields/1607","display_name":"Spectroscopy"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/docking","display_name":"Docking (animal)","score":0.6883208751678467},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.6878567337989807},{"id":"https://openalex.org/keywords/g-protein-coupled-receptor","display_name":"G protein-coupled receptor","score":0.6868192553520203},{"id":"https://openalex.org/keywords/allosteric-regulation","display_name":"Allosteric regulation","score":0.6651064157485962},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5417284965515137},{"id":"https://openalex.org/keywords/ligand","display_name":"Ligand (biochemistry)","score":0.4230741262435913},{"id":"https://openalex.org/keywords/biological-system","display_name":"Biological system","score":0.40433239936828613},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.3859892785549164},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.34259021282196045},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.337257444858551},{"id":"https://openalex.org/keywords/receptor","display_name":"Receptor","score":0.195613294839859},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.10698792338371277},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.09288695454597473}],"concepts":[{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.6883208751678467},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.6878567337989807},{"id":"https://openalex.org/C135285700","wikidata":"https://www.wikidata.org/wiki/Q38173","display_name":"G protein-coupled receptor","level":3,"score":0.6868192553520203},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.6651064157485962},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5417284965515137},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.4230741262435913},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.40433239936828613},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3859892785549164},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.34259021282196045},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.337257444858551},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.195613294839859},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.10698792338371277},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.09288695454597473},{"id":"https://openalex.org/C159110408","wikidata":"https://www.wikidata.org/wiki/Q121176","display_name":"Nursing","level":1,"score":0.0},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.0}],"mesh":[{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018343","descriptor_name":"Receptors, Adrenergic, beta-2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018343","descriptor_name":"Receptors, Adrenergic, beta-2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018343","descriptor_name":"Receptors, Adrenergic, beta-2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D043562","descriptor_name":"Receptors, G-Protein-Coupled","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D043562","descriptor_name":"Receptors, G-Protein-Coupled","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D043562","descriptor_name":"Receptors, G-Protein-Coupled","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.1c00712","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.1c00712","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:34549581","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34549581","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.7799999713897705,"display_name":"Affordable and clean energy","id":"https://metadata.un.org/sdg/7"}],"awards":[{"id":"https://openalex.org/G5358808625","display_name":null,"funder_award_id":"JP20H03229","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"}],"funders":[{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":52,"referenced_works":["https://openalex.org/W1968682237","https://openalex.org/W1976161355","https://openalex.org/W1976499671","https://openalex.org/W1977486075","https://openalex.org/W1981225934","https://openalex.org/W1990372288","https://openalex.org/W2018786413","https://openalex.org/W2022298113","https://openalex.org/W2023940150","https://openalex.org/W2032226429","https://openalex.org/W2035199159","https://openalex.org/W2035266068","https://openalex.org/W2045683699","https://openalex.org/W2047580257","https://openalex.org/W2049617698","https://openalex.org/W2052032940","https://openalex.org/W2057477511","https://openalex.org/W2059013803","https://openalex.org/W2062692230","https://openalex.org/W2081693079","https://openalex.org/W2086086905","https://openalex.org/W2103945336","https://openalex.org/W2104477830","https://openalex.org/W2118233996","https://openalex.org/W2118998349","https://openalex.org/W2147993766","https://openalex.org/W2161605421","https://openalex.org/W2165414288","https://openalex.org/W2252718331","https://openalex.org/W2323104785","https://openalex.org/W2346012195","https://openalex.org/W2404280981","https://openalex.org/W2513379522","https://openalex.org/W2517814100","https://openalex.org/W2543839061","https://openalex.org/W2604223107","https://openalex.org/W2613003159","https://openalex.org/W2747261161","https://openalex.org/W2770371168","https://openalex.org/W2886639208","https://openalex.org/W2887064975","https://openalex.org/W2899596245","https://openalex.org/W2900311838","https://openalex.org/W2915232951","https://openalex.org/W2921098500","https://openalex.org/W3003657470","https://openalex.org/W3005171368","https://openalex.org/W3014394487","https://openalex.org/W3121001695","https://openalex.org/W3134762652","https://openalex.org/W3136571708","https://openalex.org/W3161028058"],"related_works":["https://openalex.org/W2939998722","https://openalex.org/W2169750653","https://openalex.org/W2195592873","https://openalex.org/W1971782741","https://openalex.org/W3005062988","https://openalex.org/W2075777827","https://openalex.org/W4211217675","https://openalex.org/W2911329269","https://openalex.org/W2592466923","https://openalex.org/W1555254413"],"abstract_inverted_index":{"-adrenergic":[0],"receptor,":[1],"and":[2,66,94,97,116,142,164],"its":[3,48],"antagonist,":[4],"alprenolol,":[5],"using":[6],"one":[7],"of":[8,29,57,68,76,92,110,144,150,181,208,222],"the":[9,27,30,69,73,84,111,120,125,131,145,151,158,171,175,182,185,192,206,219],"enhanced":[10],"conformation":[11],"sampling":[12,72],"methods,":[13],"multicanonical":[14],"molecular":[15],"dynamics":[16],"(McMD),":[17],"which":[18,61,189],"does":[19],"not":[20],"rely":[21],"on":[22],"any":[23],"prior":[24],"knowledge":[25],"for":[26,140,184,218],"definition":[28],"reaction":[31],"coordinate.":[32],"Although":[33],"we":[34,98,203],"have":[35],"previously":[36],"applied":[37],"our":[38,104,167,209],"McMD-based":[39],"dynamic":[40],"docking":[41],"protocol":[42],"to":[43,50,156,197,214],"various":[44],"globular":[45],"protein":[46],"systems,":[47],"application":[49,207],"GPCR":[51],"systems":[52],"would":[53],"be":[54,212],"difficult":[55],"because":[56,67],"their":[58],"complicated":[59],"design,":[60],"include":[62],"a":[63,77,89,198],"lipid":[64],"bilayer,":[65],"difficulty":[70,172],"in":[71,160,173],"configurational":[74],"space":[75],"binding":[78,101,177],"site":[79],"that":[80,148,205,224],"exists":[81],"deep":[82],"inside":[83],"GPCR.":[85],"Our":[86],"simulations":[87,137],"sampled":[88],"wide":[90],"array":[91],"ligand-bound":[93],"ligand-unbound":[95],"structures,":[96,118,146],"measured":[99],"427":[100],"events":[102],"during":[103],"48":[105],"\u03bcs":[106],"production":[107],"run.":[108],"Analysis":[109],"ensemble":[112],"revealed":[113],"several":[114],"stable":[115,122,155],"meta-stable":[117],"where":[119],"most":[121,149],"structure":[123],"at":[124],"global":[126],"free":[127],"energy":[128],"minimum":[129],"matches":[130],"experimental":[132],"one.":[133],"Additional":[134],"canonical":[135],"MD":[136],"were":[138],"used":[139,213],"refinement":[141],"validation":[143],"revealing":[147],"intermediates":[152],"are":[153],"sufficiently":[154],"trap":[157],"ligand":[159],"these":[161],"intermediary":[162],"states":[163],"furthermore":[165],"validated":[166],"prediction":[168],"results.":[169],"Given":[170],"reaching":[174],"orthosteric":[176],"site,":[178],"chemical":[179],"optimization":[180],"compound":[183],"second":[186],"ranking":[187],"configuration,":[188],"binds":[190],"near":[191],"pocket's":[193],"entrance,":[194],"might":[195],"lead":[196],"high-affinity":[199],"allosteric":[200],"inhibitor.":[201],"Accordingly,":[202],"show":[204],"methodology":[210],"can":[211],"provide":[215],"crucial":[216],"insights":[217],"rational":[220],"design":[221],"drugs":[223],"target":[225],"GPCRs.":[226]},"counts_by_year":[{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":4},{"year":2021,"cited_by_count":1}],"updated_date":"2026-04-28T14:05:53.105641","created_date":"2025-10-10T00:00:00"}
