{"id":"https://openalex.org/W3045516565","doi":"https://doi.org/10.1017/cts.2020.74","title":"4558 Investigating the functional consequences of anaplastic lymphoma kinase (ALK) mutations arising upon Lorlatinib treatment","display_name":"4558 Investigating the functional consequences of anaplastic lymphoma kinase (ALK) mutations arising upon Lorlatinib treatment","publication_year":2020,"publication_date":"2020-06-01","ids":{"openalex":"https://openalex.org/W3045516565","doi":"https://doi.org/10.1017/cts.2020.74","mag":"3045516565"},"language":"en","primary_location":{"id":"doi:10.1017/cts.2020.74","doi":"https://doi.org/10.1017/cts.2020.74","is_oa":true,"landing_page_url":"https://doi.org/10.1017/cts.2020.74","pdf_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9F7F5676BB5B458DD47B5399107D6360/S2059866120000746a.pdf/div-class-title-4558-investigating-the-functional-consequences-of-anaplastic-lymphoma-kinase-alk-mutations-arising-upon-lorlatinib-treatment-div.pdf","source":{"id":"https://openalex.org/S4210205013","display_name":"Journal of Clinical and Translational Science","issn_l":"2059-8661","issn":["2059-8661"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","ki-jl-1","poland-20","russia-white-list-2"],"host_organization":"https://openalex.org/P4310311721","host_organization_name":"Cambridge University Press","host_organization_lineage":["https://openalex.org/P4310311721","https://openalex.org/P4310311702"],"host_organization_lineage_names":["Cambridge University Press","University of Cambridge"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical and Translational Science","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9F7F5676BB5B458DD47B5399107D6360/S2059866120000746a.pdf/div-class-title-4558-investigating-the-functional-consequences-of-anaplastic-lymphoma-kinase-alk-mutations-arising-upon-lorlatinib-treatment-div.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5033896871","display_name":"Gabriela M. Witek","orcid":"https://orcid.org/0000-0003-2635-773X","observed_orcids":["https://orcid.org/0000-0003-2635-773X"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gabriela Maria Witek","raw_affiliation_strings":["University of Pennsylvania School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania School of Medicine","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081692917","display_name":"Whelton A. Miller","orcid":"https://orcid.org/0000-0003-3822-7940","observed_orcids":["https://orcid.org/0000-0003-3822-7940"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Whelton Miller","raw_affiliation_strings":["University of Pennsylvania School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania School of Medicine","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090325434","display_name":"David R. Slochower","orcid":"https://orcid.org/0000-0003-3928-5050","observed_orcids":["https://orcid.org/0000-0003-3928-5050"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Slochower","raw_affiliation_strings":["University of Pennsylvania School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania School of Medicine","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010980492","display_name":"Esther R. Berko","orcid":"https://orcid.org/0000-0001-7181-1378","observed_orcids":["https://orcid.org/0000-0001-7181-1378"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Esther Berko","raw_affiliation_strings":["University of Pennsylvania School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania School of Medicine","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5030496565","display_name":"Ya\u00ebl P. Moss\u00e9","orcid":"https://orcid.org/0000-0002-3463-0399","observed_orcids":["https://orcid.org/0000-0002-3463-0399"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yael Moss\u00e9","raw_affiliation_strings":["University of Pennsylvania School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania School of Medicine","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073959537","display_name":"Mark A. Lemmon","orcid":"https://orcid.org/0000-0002-3379-5319","observed_orcids":["https://orcid.org/0000-0002-3379-5319"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mark Lemmon","raw_affiliation_strings":["University of Pennsylvania School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania School of Medicine","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5037007496","display_name":"Ravi Radhakrishnan","orcid":"https://orcid.org/0000-0003-0686-2851","observed_orcids":["https://orcid.org/0000-0003-0686-2851"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ravi Radhakrishnan","raw_affiliation_strings":["University of Pennsylvania School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania School of Medicine","institution_ids":["https://openalex.org/I79576946"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I79576946"],"apc_list":{"value":1750,"currency":"USD","value_usd":1750},"apc_paid":{"value":1750,"currency":"USD","value_usd":1750},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.10202232,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"4","issue":"s1","first_page":"9","last_page":"10"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12226","display_name":"Neuroblastoma Research and Treatments","score":0.5684000253677368,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"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/T12226","display_name":"Neuroblastoma Research and Treatments","score":0.5684000253677368,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.3984000086784363,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T11173","display_name":"Neurofibromatosis and Schwannoma Cases","score":0.00139999995008111,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/anaplastic-lymphoma-kinase","display_name":"anaplastic lymphoma kinase","score":0.8870000243186951},{"id":"https://openalex.org/keywords/lorlatinib","display_name":"lorlatinib","score":0.8429999947547913},{"id":"https://openalex.org/keywords/neuroblastoma","display_name":"neuroblastoma","score":0.9359999895095825},{"id":"https://openalex.org/keywords/alk-mutations","display_name":"ALK mutations","score":0.8870000243186951},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.7960000038146973},{"id":"https://openalex.org/keywords/compound-mutations","display_name":"compound mutations","score":0.8450000286102295},{"id":"https://openalex.org/keywords/atp-binding","display_name":"ATP binding","score":0.5849999785423279},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitors","display_name":"tyrosine kinase inhibitors","score":0.7440000176429749},{"id":"https://openalex.org/keywords/molecular-docking","display_name":"molecular docking","score":0.6309999823570251},{"id":"https://openalex.org/keywords/molecular-dynamics-simulation","display_name":"molecular dynamics simulation","score":0.7580000162124634},{"id":"https://openalex.org/keywords/computational-structural-biology","display_name":"computational structural biology","score":0.5699999928474426},{"id":"https://openalex.org/keywords/targeted-therapy","display_name":"targeted therapy","score":0.6039999723434448},{"id":"https://openalex.org/keywords/binding-affinity","display_name":"binding affinity","score":0.45100000500679016},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.453000009059906}],"concepts":[{"id":"https://openalex.org/C117643217","wikidata":"https://www.wikidata.org/wiki/Q17824987","display_name":"Anaplastic lymphoma kinase","level":4,"score":0.9408936500549316},{"id":"https://openalex.org/C2779422266","wikidata":"https://www.wikidata.org/wiki/Q5186964","display_name":"Crizotinib","level":4,"score":0.9206905364990234},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7187276482582092},{"id":"https://openalex.org/C2778347629","wikidata":"https://www.wikidata.org/wiki/Q4652380","display_name":"ALK inhibitor","level":5,"score":0.6561895608901978},{"id":"https://openalex.org/C2776715637","wikidata":"https://www.wikidata.org/wiki/Q938205","display_name":"Neuroblastoma","level":3,"score":0.5625799894332886},{"id":"https://openalex.org/C2778820342","wikidata":"https://www.wikidata.org/wiki/Q906415","display_name":"Tyrosine-kinase inhibitor","level":3,"score":0.521250307559967},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.5212188959121704},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4960509240627289},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4503239691257477},{"id":"https://openalex.org/C2781230642","wikidata":"https://www.wikidata.org/wiki/Q492646","display_name":"Targeted therapy","level":3,"score":0.43442195653915405},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.3782498240470886},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3690112829208374},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3431817889213562},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2510243058204651},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2409723699092865},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.23892873525619507},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.09270307421684265},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.08789360523223877},{"id":"https://openalex.org/C2776232967","wikidata":"https://www.wikidata.org/wiki/Q6743514","display_name":"Malignant pleural effusion","level":3,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.1017/cts.2020.74","doi":"https://doi.org/10.1017/cts.2020.74","is_oa":true,"landing_page_url":"https://doi.org/10.1017/cts.2020.74","pdf_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9F7F5676BB5B458DD47B5399107D6360/S2059866120000746a.pdf/div-class-title-4558-investigating-the-functional-consequences-of-anaplastic-lymphoma-kinase-alk-mutations-arising-upon-lorlatinib-treatment-div.pdf","source":{"id":"https://openalex.org/S4210205013","display_name":"Journal of Clinical and Translational Science","issn_l":"2059-8661","issn":["2059-8661"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","ki-jl-1","poland-20","russia-white-list-2"],"host_organization":"https://openalex.org/P4310311721","host_organization_name":"Cambridge University Press","host_organization_lineage":["https://openalex.org/P4310311721","https://openalex.org/P4310311702"],"host_organization_lineage_names":["Cambridge University Press","University of Cambridge"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical and Translational Science","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8823389","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8823389","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"J Clin Transl Sci","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:d9d8910bcb614399b7b21266319c825a","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/d9d8910bcb614399b7b21266319c825a","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Journal of Clinical and Translational Science, Vol 4, Pp 9-10 (2020)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.1017/cts.2020.74","doi":"https://doi.org/10.1017/cts.2020.74","is_oa":true,"landing_page_url":"https://doi.org/10.1017/cts.2020.74","pdf_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9F7F5676BB5B458DD47B5399107D6360/S2059866120000746a.pdf/div-class-title-4558-investigating-the-functional-consequences-of-anaplastic-lymphoma-kinase-alk-mutations-arising-upon-lorlatinib-treatment-div.pdf","source":{"id":"https://openalex.org/S4210205013","display_name":"Journal of Clinical and Translational Science","issn_l":"2059-8661","issn":["2059-8661"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","ki-jl-1","poland-20","russia-white-list-2"],"host_organization":"https://openalex.org/P4310311721","host_organization_name":"Cambridge University Press","host_organization_lineage":["https://openalex.org/P4310311721","https://openalex.org/P4310311702"],"host_organization_lineage_names":["Cambridge University Press","University of Cambridge"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical and Translational Science","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.98580002784729,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W3045516565.pdf","grobid_xml":"https://content.openalex.org/works/W3045516565.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3175790027","https://openalex.org/W4393097120","https://openalex.org/W2887622849","https://openalex.org/W171311624","https://openalex.org/W4407150349","https://openalex.org/W2146396128","https://openalex.org/W2739890533","https://openalex.org/W6940882746","https://openalex.org/W4372294503","https://openalex.org/W7161585550"],"abstract_inverted_index":{"OBJECTIVES/GOALS:":[0],"Neuroblastoma":[1],"(NB)":[2],"is":[3],"an":[4,187],"embryonal":[5],"cancer":[6,185],"of":[7,43,93,99,123,133,171,201,210,258,297,315,395,402,405,413],"the":[8,89,96,113,120,124,134,199,219,250,254,302,312,316,327,342,355,359,364,369,388,400,403,411,428],"sympathetic":[9],"nervous":[10],"system":[11],"that":[12,108,156,214,341],"affects":[13],"mostly":[14],"infants":[15],"and":[16,32,48,102,104,150,190,222,224,263,278,289,304,330,334,382,409,422],"young":[17],"children.":[18],"The":[19,393],"complex":[20,240],"genetic":[21],"background":[22],"present":[23],"across":[24],"NB":[25,38,146,194],"patients":[26,39,143,180,192],"results":[27,394],"in":[28,34,67,119,142,168,179,191,239,274,308,332,373],"diverse":[29],"clinical":[30,175],"response":[31],"difficulty":[33],"individualizing":[35],"therapy.":[36],"Currently,":[37],"undergo":[40],"a":[41,75,127,158,208,232],"regimen":[42],"genotoxic":[44],"chemotherapeutics,":[45],"radiation":[46],"therapy,":[47],"new":[49,251,414],"immunotherapy":[50],"that,":[51],"while":[52],"effective,":[53],"has":[54],"significant":[55],"side":[56],"effects,":[57],"including":[58],"excruciating":[59],"pain.":[60],"One":[61],"promising":[62],"avenue":[63],"for":[64,354,361],"targeted":[65],"therapy":[66],"neuroblastoma":[68],"focuses":[69],"on":[70,283,293],"anaplastic":[71],"lymphoma":[72],"kinase":[73,91],"(ALK),":[74],"cell":[76,183],"surface":[77],"neural":[78],"receptor":[79],"tyrosine":[80,90,136],"kinase.":[81],"We":[82,153,212,271,339],"previously":[83],"identified":[84],"activating":[85],"point":[86],"mutations":[87,118,197,206,217,252,303,344,366],"within":[88],"domain":[92],"ALK":[94,135,148,161,188,196,205,223,238,267,376,415],"as":[95,207,243,245,318,320],"primary":[97],"cause":[98,225,265,345],"hereditary":[100],"NB,":[101],"we":[103,230,300],"others":[105],"subsequently":[106],"showed":[107,138],"these":[109,215],"same":[110],"alterations":[111],"are":[112],"most":[114],"common":[115],"somatic":[116],"single-nucleotide":[117],"sporadic":[121],"forms":[122],"disease.":[125],"Crizotinib,":[126],"first-generation":[128],"small":[129],"molecule":[130],"ATP-competitive":[131,160],"inhibitor":[132],"kinase,":[137],"limited":[139],"anti-tumor":[140],"activity":[141],"with":[144,177,181,193,241],"relapsed":[145],"harboring":[147,186,195],"F1174":[149],"F1245":[151],"mutations.":[152],"have":[154],"demonstrated":[155],"lorlatinib,":[157],"novel":[159],"inhibitor,":[162],"overcomes":[163],"this":[164,228,396],"de":[165],"novo":[166],"resistance":[167,346,406],"preclinical":[169],"models":[170],"ALK-driven":[172],"NB.":[173],"Recent":[174],"trials":[176],"lorlatinib":[178,242,348,408],"non-small":[182],"lung":[184],"fusion,":[189],"show":[198],"emergence":[200],"multiple":[202],"or":[203,256,357,417],"compound":[204,216,343,365],"mechanism":[209,404],"resistance.":[211,226,389,429],"postulate":[213],"disrupt":[218,368],"interaction":[220],"between":[221],"In":[227],"study,":[229],"employ":[231,272],"computational":[233,275],"approach":[234],"to":[235,247,261,310,325,347,407,426],"model":[236,301],"mutated":[237],"well":[244,319],"ATP":[246],"understand":[248],"whether":[249],"alter":[253],"affinity":[255,353,360],"mode":[257],"lorlatinib/ATP":[259],"binding":[260,328],"ALK,":[262,299],"thus":[264],"suboptimal":[266],"inhibition.":[268],"METHODS/STUDY":[269],"POPULATION:":[270],"methods":[273],"structural":[276],"biology":[277],"drug":[279,356],"design,":[280],"primarily":[281],"based":[282],"molecular":[284,286,290],"modeling,":[285],"dynamics":[287],"(MD),":[288],"docking.":[291],"Based":[292],"existing":[294],"crystal":[295],"structures":[296],"wildtype":[298],"perform":[305,321],"MD":[306],"simulations":[307],"order":[309],"characterize":[311],"activation":[313,371],"state":[314],"protein":[317,352,370],"ensemble":[322],"docking":[323],"calculations":[324],"assess":[326],"affinities":[329],"modes":[331],"ALK-lorlatinib":[333],"ALK-ATP":[335],"complexes.":[336],"RESULTS/ANTICIPATED":[337],"RESULTS:":[338],"expect":[340],"either":[349],"by":[350],"lowering":[351],"increasing":[358],"ATP.":[362],"Alternatively,":[363],"may":[367,377],"state,":[372],"which":[374],"case":[375],"no":[378],"longer":[379],"be":[380,386],"active,":[381],"another":[383],"protein/pathway":[384],"could":[385],"driving":[387],"DISCUSSION/SIGNIFICANCE":[390],"OF":[391],"IMPACT:":[392],"study":[397],"will":[398],"enable":[399],"understanding":[401],"facilitate":[410],"design":[412],"inhibitors,":[416],"help":[418],"develop":[419],"more":[420],"optimal":[421],"mechanism-guided":[423],"therapies":[424],"aimed":[425],"overcome":[427]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2020-08-03T00:00:00"}