{"id":"https://openalex.org/W2396925637","doi":"https://doi.org/10.1021/acs.jcim.5b00270","title":"Structural Stability and Flexibility Direct the Selection of Activating Mutations in Epidermal Growth Factor Receptor Kinase","display_name":"Structural Stability and Flexibility Direct the Selection of Activating Mutations in Epidermal Growth Factor Receptor Kinase","publication_year":2015,"publication_date":"2015-06-29","ids":{"openalex":"https://openalex.org/W2396925637","doi":"https://doi.org/10.1021/acs.jcim.5b00270","mag":"2396925637","pmid":"https://pubmed.ncbi.nlm.nih.gov/26121158"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5b00270","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5b00270","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/A5077813943","display_name":"Antonella Paladino","orcid":"https://orcid.org/0000-0002-9397-1572"},"institutions":[{"id":"https://openalex.org/I4210109941","display_name":"Institute of Chemistry of Molecular Recognition","ror":"https://ror.org/0141vn777","country_code":"IT","type":"facility","lineage":["https://openalex.org/I4210109941","https://openalex.org/I4210155236"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Antonella Paladino","raw_affiliation_strings":["Istituto di Chimica del Riconoscimento Molecolare, CNR Via Mario Bianco 9, 20131, Milano, Italy"],"affiliations":[{"raw_affiliation_string":"Istituto di Chimica del Riconoscimento Molecolare, CNR Via Mario Bianco 9, 20131, Milano, Italy","institution_ids":["https://openalex.org/I4210109941"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064391171","display_name":"Giulia Morra","orcid":"https://orcid.org/0000-0002-9681-7845"},"institutions":[{"id":"https://openalex.org/I4210109941","display_name":"Institute of Chemistry of Molecular Recognition","ror":"https://ror.org/0141vn777","country_code":"IT","type":"facility","lineage":["https://openalex.org/I4210109941","https://openalex.org/I4210155236"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Giulia Morra","raw_affiliation_strings":["Istituto di Chimica del Riconoscimento Molecolare, CNR Via Mario Bianco 9, 20131, Milano, Italy"],"affiliations":[{"raw_affiliation_string":"Istituto di Chimica del Riconoscimento Molecolare, CNR Via Mario Bianco 9, 20131, Milano, Italy","institution_ids":["https://openalex.org/I4210109941"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5046491394","display_name":"Giorgio Colombo","orcid":"https://orcid.org/0000-0002-1318-668X"},"institutions":[{"id":"https://openalex.org/I4210109941","display_name":"Institute of Chemistry of Molecular Recognition","ror":"https://ror.org/0141vn777","country_code":"IT","type":"facility","lineage":["https://openalex.org/I4210109941","https://openalex.org/I4210155236"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Giorgio Colombo","raw_affiliation_strings":["Istituto di Chimica del Riconoscimento Molecolare, CNR Via Mario Bianco 9, 20131, Milano, Italy"],"affiliations":[{"raw_affiliation_string":"Istituto di Chimica del Riconoscimento Molecolare, CNR Via Mario Bianco 9, 20131, Milano, Italy","institution_ids":["https://openalex.org/I4210109941"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5077813943"],"corresponding_institution_ids":["https://openalex.org/I4210109941"],"apc_list":null,"apc_paid":null,"fwci":1.126,"has_fulltext":false,"cited_by_count":29,"citation_normalized_percentile":{"value":0.80577907,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":98},"biblio":{"volume":"55","issue":"7","first_page":"1377","last_page":"1387"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.9988999962806702,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.9988999962806702,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9986000061035156,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10602","display_name":"Glycosylation and Glycoproteins Research","score":0.9984999895095825,"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/context","display_name":"Context (archaeology)","score":0.6230331063270569},{"id":"https://openalex.org/keywords/mutant","display_name":"Mutant","score":0.5761575102806091},{"id":"https://openalex.org/keywords/epidermal-growth-factor-receptor","display_name":"Epidermal growth factor receptor","score":0.5372971892356873},{"id":"https://openalex.org/keywords/point-mutation","display_name":"Point mutation","score":0.5072276592254639},{"id":"https://openalex.org/keywords/scaffold-protein","display_name":"Scaffold protein","score":0.500725507736206},{"id":"https://openalex.org/keywords/cell-biology","display_name":"Cell biology","score":0.4727120101451874},{"id":"https://openalex.org/keywords/mutation","display_name":"Mutation","score":0.4692022204399109},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.4607222378253937},{"id":"https://openalex.org/keywords/protein-structure","display_name":"Protein structure","score":0.45710524916648865},{"id":"https://openalex.org/keywords/protein-kinase-a","display_name":"Protein kinase A","score":0.4553835690021515},{"id":"https://openalex.org/keywords/kinase","display_name":"Kinase","score":0.45143797993659973},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.3951113820075989},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.3373589515686035},{"id":"https://openalex.org/keywords/genetics","display_name":"Genetics","score":0.2947489619255066},{"id":"https://openalex.org/keywords/receptor","display_name":"Receptor","score":0.2925155758857727},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.27071139216423035},{"id":"https://openalex.org/keywords/signal-transduction","display_name":"Signal transduction","score":0.2603970170021057},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.12532293796539307}],"concepts":[{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.6230331063270569},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.5761575102806091},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.5372971892356873},{"id":"https://openalex.org/C176944494","wikidata":"https://www.wikidata.org/wiki/Q1415380","display_name":"Point mutation","level":4,"score":0.5072276592254639},{"id":"https://openalex.org/C53645450","wikidata":"https://www.wikidata.org/wiki/Q907093","display_name":"Scaffold protein","level":3,"score":0.500725507736206},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4727120101451874},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4692022204399109},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4607222378253937},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.45710524916648865},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.4553835690021515},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.45143797993659973},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3951113820075989},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3373589515686035},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2947489619255066},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.2925155758857727},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.27071139216423035},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2603970170021057},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.12532293796539307},{"id":"https://openalex.org/C151730666","wikidata":"https://www.wikidata.org/wiki/Q7205","display_name":"Paleontology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004789","descriptor_name":"Enzyme Activation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004789","descriptor_name":"Enzyme Activation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004789","descriptor_name":"Enzyme Activation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004795","descriptor_name":"Enzyme Stability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004795","descriptor_name":"Enzyme Stability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004795","descriptor_name":"Enzyme Stability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"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":"D017434","descriptor_name":"Protein Structure, Tertiary","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017434","descriptor_name":"Protein Structure, Tertiary","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017434","descriptor_name":"Protein Structure, Tertiary","qualifier_ui":null,"qualifier_name":null,"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":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5b00270","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5b00270","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:26121158","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/26121158","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":[],"awards":[{"id":"https://openalex.org/G3883042724","display_name":null,"funder_award_id":"2011.1800","funder_id":"https://openalex.org/F4320321499","funder_display_name":"Fondazione Cariplo"},{"id":"https://openalex.org/G5989797991","display_name":null,"funder_award_id":"IG 15420","funder_id":"https://openalex.org/F4320323054","funder_display_name":"Associazione Italiana per la Ricerca sul Cancro"}],"funders":[{"id":"https://openalex.org/F4320321499","display_name":"Fondazione Cariplo","ror":"https://ror.org/01gb56c55"},{"id":"https://openalex.org/F4320323054","display_name":"Associazione Italiana per la Ricerca sul Cancro","ror":"https://ror.org/02g2x7380"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":39,"referenced_works":["https://openalex.org/W1964217341","https://openalex.org/W1966078827","https://openalex.org/W1968324646","https://openalex.org/W1969939692","https://openalex.org/W1970174659","https://openalex.org/W1976499671","https://openalex.org/W1984467737","https://openalex.org/W1988467551","https://openalex.org/W1990526350","https://openalex.org/W1992784105","https://openalex.org/W1992945955","https://openalex.org/W2004349079","https://openalex.org/W2006184433","https://openalex.org/W2008753475","https://openalex.org/W2013226867","https://openalex.org/W2023568503","https://openalex.org/W2027539373","https://openalex.org/W2030205108","https://openalex.org/W2034975420","https://openalex.org/W2042553090","https://openalex.org/W2043224156","https://openalex.org/W2046151919","https://openalex.org/W2049888624","https://openalex.org/W2059715478","https://openalex.org/W2067174909","https://openalex.org/W2080601747","https://openalex.org/W2097097666","https://openalex.org/W2097164795","https://openalex.org/W2100794900","https://openalex.org/W2102140136","https://openalex.org/W2131288855","https://openalex.org/W2136931941","https://openalex.org/W2142544064","https://openalex.org/W2145317354","https://openalex.org/W2159705141","https://openalex.org/W2171556594","https://openalex.org/W2322778987","https://openalex.org/W2333891964","https://openalex.org/W4246043393"],"related_works":["https://openalex.org/W2160983714","https://openalex.org/W2035348284","https://openalex.org/W1926203904","https://openalex.org/W3083919238","https://openalex.org/W2047924500","https://openalex.org/W2383571109","https://openalex.org/W2264903906","https://openalex.org/W1602476250","https://openalex.org/W2059550303","https://openalex.org/W1583255772"],"abstract_inverted_index":{"Herein":[0],"we":[1],"investigate":[2],"the":[3,16,21,25,58,72,83,94,101,110,116,124,127,138,144,147,162,165,169,180,186,189,202],"potential":[4],"of":[5,8,27,47,96,126,135,146,164,171,182,204],"novel":[6],"methods":[7],"molecular":[9],"dynamics":[10,52],"analysis":[11,46],"to":[12,76,100,168],"provide":[13],"information":[14],"on":[15],"key":[17,157],"factors":[18],"that":[19,109],"underlie":[20],"preferential":[22],"localization":[23],"and":[24,50,65,79,142,176,197],"effects":[26,203],"mutations":[28,98,205],"modulating":[29,105,207],"protein":[30,48,106,111,128],"activities.":[31,209],"Epidermal":[32],"growth":[33],"factor":[34],"receptor":[35],"(EGFR)":[36],"kinases":[37],"are":[38],"selected":[39],"as":[40],"a":[41,54,62,77,195],"test":[42],"case.":[43],"The":[44,85],"combined":[45,75],"energetics":[49],"internal":[51],"indicates":[53],"clear":[55],"polarization":[56],"in":[57,68,87,137,143,155,160,179,185,206],"native":[59],"protein,":[60],"whereby":[61],"highly":[63],"stable":[64],"ordered":[66],"scaffold":[67],"one":[69],"domain,":[70,82],"namely":[71],"C-lobe,":[73],"is":[74],"flexible":[78],"loosely":[80],"stabilized":[81],"N-lobe.":[84,102],"subdivision":[86],"two":[88],"portions":[89],"with":[90],"different":[91],"properties":[92],"directs":[93],"presence":[95,145],"point":[97],"mainly":[99],"This":[103],"allows":[104],"flexibility":[107,153],"so":[108],"can":[112],"more":[113],"efficiently":[114],"sample":[115],"conformations":[117],"necessary":[118],"for":[119,188],"substrate":[120,172],"recognition,":[121],"while":[122],"leaving":[123],"stability":[125],"unperturbed.":[129],"In":[130],"this":[131],"context,":[132],"comparative":[133],"simulations":[134],"EGFR":[136],"wild":[139],"type":[140],"sequence":[141],"activating":[148],"oncogenic":[149],"mutation":[150],"G719S":[151],"reveal":[152],"changes":[154],"several":[156],"regions,":[158],"involving":[159],"particular":[161],"part":[163],"kinase":[166],"devoted":[167],"regulation":[170],"recognition":[173],"(regulatory":[174],"core)":[175],"an":[177],"increase":[178],"number":[181],"stabilizing":[183],"interactions":[184],"N-lobe":[187],"activated":[190],"mutant.":[191],"Our":[192],"approaches":[193],"represent":[194],"promising":[196],"simple":[198],"strategy":[199],"toward":[200],"rationalizing":[201],"enzymatic":[208]},"counts_by_year":[{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":4},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":3},{"year":2019,"cited_by_count":5},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":4},{"year":2016,"cited_by_count":2}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}
