{"id":"https://openalex.org/W2575009204","doi":"https://doi.org/10.1021/acs.jcim.6b00679","title":"Metadynamics Simulations Distinguish Short- and Long-Residence-Time Inhibitors of Cyclin-Dependent Kinase 8","display_name":"Metadynamics Simulations Distinguish Short- and Long-Residence-Time Inhibitors of Cyclin-Dependent Kinase 8","publication_year":2017,"publication_date":"2017-01-12","ids":{"openalex":"https://openalex.org/W2575009204","doi":"https://doi.org/10.1021/acs.jcim.6b00679","mag":"2575009204","pmid":"https://pubmed.ncbi.nlm.nih.gov/28080056"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.6b00679","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6b00679","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/A5003793222","display_name":"Donatella Callegari","orcid":"https://orcid.org/0000-0002-2574-3826"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Donatella Callegari","raw_affiliation_strings":["Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy"],"raw_orcid":"https://orcid.org/0000-0002-2574-3826","affiliations":[{"raw_affiliation_string":"Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042341429","display_name":"Alessio Lodola","orcid":"https://orcid.org/0000-0002-8675-1002"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Alessio Lodola","raw_affiliation_strings":["Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy"],"raw_orcid":"https://orcid.org/0000-0002-8675-1002","affiliations":[{"raw_affiliation_string":"Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067645091","display_name":"Daniele Pala","orcid":"https://orcid.org/0000-0001-6160-6127"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Daniele Pala","raw_affiliation_strings":["Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy"],"raw_orcid":"https://orcid.org/0000-0001-6160-6127","affiliations":[{"raw_affiliation_string":"Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042136064","display_name":"Silvia Rivara","orcid":"https://orcid.org/0000-0001-8058-4250"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Silvia Rivara","raw_affiliation_strings":["Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy"],"raw_orcid":"https://orcid.org/0000-0001-8058-4250","affiliations":[{"raw_affiliation_string":"Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085013575","display_name":"Marco Mor","orcid":"https://orcid.org/0000-0003-0199-1849"},"institutions":[{"id":"https://openalex.org/I124601658","display_name":"University of Parma","ror":"https://ror.org/02k7wn190","country_code":"IT","type":"education","lineage":["https://openalex.org/I124601658"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Marco Mor","raw_affiliation_strings":["Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy"],"raw_orcid":"https://orcid.org/0000-0003-0199-1849","affiliations":[{"raw_affiliation_string":"Dipartimento\rdi Farmacia, Universit\u00e0 degli Studi di Parma, Viale delle\rscienze 27/A, 43124 Parma, Italy","institution_ids":["https://openalex.org/I124601658"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026440664","display_name":"Andrea Rizzi","orcid":"https://orcid.org/0000-0001-7693-2013"},"institutions":[{"id":"https://openalex.org/I4210162628","display_name":"Chiesi (Italy)","ror":"https://ror.org/0511bn634","country_code":"IT","type":"company","lineage":["https://openalex.org/I4210162628"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Andrea Rizzi","raw_affiliation_strings":["Chemistry\rResearch and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemistry\rResearch and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy","institution_ids":["https://openalex.org/I4210162628"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5045419617","display_name":"Anna Maria Capelli","orcid":null},"institutions":[{"id":"https://openalex.org/I4210162628","display_name":"Chiesi (Italy)","ror":"https://ror.org/0511bn634","country_code":"IT","type":"company","lineage":["https://openalex.org/I4210162628"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Anna Maria Capelli","raw_affiliation_strings":["Chemistry\rResearch and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemistry\rResearch and Drug Design Department, Chiesi Farmaceutici S.p.A., Largo F. Belloli 11/A, 43122 Parma, Italy","institution_ids":["https://openalex.org/I4210162628"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5003793222"],"corresponding_institution_ids":["https://openalex.org/I124601658"],"apc_list":null,"apc_paid":null,"fwci":3.7059,"has_fulltext":false,"cited_by_count":66,"citation_normalized_percentile":{"value":0.93964255,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":94,"max":99},"biblio":{"volume":"57","issue":"2","first_page":"159","last_page":"169"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9957000017166138,"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":0.9957000017166138,"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/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.9937000274658203,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.993399977684021,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/metadynamics","display_name":"Metadynamics","score":0.5936568975448608},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.4868430495262146},{"id":"https://openalex.org/keywords/biological-system","display_name":"Biological system","score":0.48291847109794617},{"id":"https://openalex.org/keywords/residence-time","display_name":"Residence time (fluid dynamics)","score":0.4603099822998047},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.4290006458759308},{"id":"https://openalex.org/keywords/statistical-physics","display_name":"Statistical physics","score":0.42687517404556274},{"id":"https://openalex.org/keywords/drug-discovery","display_name":"Drug discovery","score":0.4265159070491791},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.3023017644882202},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.2834553122520447},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.2827797532081604},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.17717388272285461},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.11506828665733337}],"concepts":[{"id":"https://openalex.org/C62752575","wikidata":"https://www.wikidata.org/wiki/Q6822487","display_name":"Metadynamics","level":3,"score":0.5936568975448608},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4868430495262146},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.48291847109794617},{"id":"https://openalex.org/C2775913793","wikidata":"https://www.wikidata.org/wiki/Q3030793","display_name":"Residence time (fluid dynamics)","level":2,"score":0.4603099822998047},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4290006458759308},{"id":"https://openalex.org/C121864883","wikidata":"https://www.wikidata.org/wiki/Q677916","display_name":"Statistical physics","level":1,"score":0.42687517404556274},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.4265159070491791},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.3023017644882202},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.2834553122520447},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.2827797532081604},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.17717388272285461},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.11506828665733337},{"id":"https://openalex.org/C187320778","wikidata":"https://www.wikidata.org/wiki/Q1349130","display_name":"Geotechnical engineering","level":1,"score":0.0},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.0}],"mesh":[{"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":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"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":"D056850","descriptor_name":"Cyclin-Dependent Kinase 8","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D056850","descriptor_name":"Cyclin-Dependent Kinase 8","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D056850","descriptor_name":"Cyclin-Dependent Kinase 8","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D056850","descriptor_name":"Cyclin-Dependent Kinase 8","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D056850","descriptor_name":"Cyclin-Dependent Kinase 8","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D056850","descriptor_name":"Cyclin-Dependent Kinase 8","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.6b00679","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6b00679","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:28080056","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/28080056","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":[{"id":"https://metadata.un.org/sdg/3","score":0.41999998688697815,"display_name":"Good health and well-being"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":40,"referenced_works":["https://openalex.org/W163215353","https://openalex.org/W1230652463","https://openalex.org/W1525531613","https://openalex.org/W1975732928","https://openalex.org/W1985588649","https://openalex.org/W1987048011","https://openalex.org/W1992899488","https://openalex.org/W1994941561","https://openalex.org/W1999522888","https://openalex.org/W2001357862","https://openalex.org/W2005006118","https://openalex.org/W2012529917","https://openalex.org/W2016408686","https://openalex.org/W2030718808","https://openalex.org/W2032427406","https://openalex.org/W2035527380","https://openalex.org/W2057806291","https://openalex.org/W2057980421","https://openalex.org/W2063945425","https://openalex.org/W2067174909","https://openalex.org/W2082586732","https://openalex.org/W2083128709","https://openalex.org/W2085829368","https://openalex.org/W2099598754","https://openalex.org/W2101077350","https://openalex.org/W2130212172","https://openalex.org/W2133620840","https://openalex.org/W2133641393","https://openalex.org/W2149141089","https://openalex.org/W2149655632","https://openalex.org/W2159497832","https://openalex.org/W2167468911","https://openalex.org/W2207535250","https://openalex.org/W2271736303","https://openalex.org/W2287402248","https://openalex.org/W2313946970","https://openalex.org/W2321825159","https://openalex.org/W2346925722","https://openalex.org/W2404651707","https://openalex.org/W2414725821"],"related_works":["https://openalex.org/W2599759970","https://openalex.org/W1633592986","https://openalex.org/W1979607105","https://openalex.org/W4385857439","https://openalex.org/W1970701509","https://openalex.org/W2020879467","https://openalex.org/W4249231514","https://openalex.org/W2964991806","https://openalex.org/W1964002518","https://openalex.org/W3131999517"],"abstract_inverted_index":{"The":[0,96,173],"duration":[1],"of":[2,18,24,34,48,81,98,105,127,150,162,185,195,206],"drug":[3,19],"efficacy":[4],"in":[5,59],"vivo":[6],"is":[7,51,157,180],"a":[8,35,67,115,153,160],"key":[9],"aspect":[10],"primarily":[11],"addressed":[12],"during":[13],"the":[14,22,31,45,60,77,103,106,109,119,125,128,151,167,183,186,190],"lead":[15],"optimization":[16],"phase":[17],"discovery.":[20],"Hence,":[21],"availability":[23],"robust":[25],"computational":[26],"approaches":[27],"that":[28,72],"can":[29],"predict":[30],"residence":[32,79,214],"time":[33,174],"compound":[36],"at":[37],"its":[38],"target":[39],"would":[40],"accelerate":[41],"candidate":[42],"selection.":[43],"Nowadays":[44],"theoretical":[46],"prediction":[47],"this":[49,178,196],"parameter":[50],"still":[52],"very":[53],"challenging.":[54],"Starting":[55],"from":[56,108],"methods":[57,100],"reported":[58,99],"literature,":[61],"we":[62],"set":[63],"up":[64],"and":[65,136,147,212],"validated":[66],"new":[68],"metadynamics":[69],"(META-D)-based":[70],"protocol":[71,123],"was":[73],"used":[74],"to":[75,176,182],"rank":[76],"experimental":[78,120],"times":[80],"10":[82],"arylpyrazole":[83],"cyclin-dependent":[84],"kinase":[85],"8":[86],"(CDK8)":[87],"inhibitors":[88,208],"for":[89,133,198],"which":[90],"target-bound":[91],"X-ray":[92],"structures":[93],"are":[94],"available.":[95],"application":[97],"based":[101],"on":[102],"detection":[104],"escape":[107],"first":[110],"free":[111],"energy":[112],"well":[113],"gave":[114],"poor":[116],"correlation":[117],"with":[118],"values.":[121],"Our":[122],"evaluates":[124],"energetics":[126],"whole":[129],"unbinding":[130],"process,":[131],"accounting":[132],"multiple":[134],"intermediates":[135],"transition":[137],"states.":[138],"Using":[139],"seven":[140],"collective":[141],"variables":[142],"(CVs)":[143],"encoding":[144],"both":[145],"roto-translational":[146],"conformational":[148],"motions":[149],"ligand,":[152],"history-dependent":[154],"biasing":[155],"potential":[156,188],"deposited":[158,187],"as":[159],"sum":[161],"constant-height":[163],"Gaussian":[164],"functions":[165],"until":[166],"ligand":[168],"reaches":[169],"an":[170,203],"unbound":[171],"state.":[172],"required":[175],"achieve":[177],"state":[179],"proportional":[181],"integral":[184],"over":[189],"CV":[191],"hyperspace.":[192],"Average":[193],"values":[194],"time,":[197],"replicated":[199],"META-D":[200],"simulations,":[201],"provided":[202],"accurate":[204],"classification":[205],"CDK8":[207],"spanning":[209],"short,":[210],"medium,":[211],"long":[213],"times.":[215]},"counts_by_year":[{"year":2026,"cited_by_count":3},{"year":2025,"cited_by_count":6},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":7},{"year":2022,"cited_by_count":6},{"year":2021,"cited_by_count":10},{"year":2020,"cited_by_count":9},{"year":2019,"cited_by_count":8},{"year":2018,"cited_by_count":9},{"year":2017,"cited_by_count":6}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}