{"id":"https://openalex.org/W7168121075","doi":"https://doi.org/10.1021/acs.jcim.6c00768","title":"Protein Language Model-Based Fitness Estimates Facilitate Resistance Mutation Identification","display_name":"Protein Language Model-Based Fitness Estimates Facilitate Resistance Mutation Identification","publication_year":2026,"publication_date":"2026-07-13","ids":{"openalex":"https://openalex.org/W7168121075","doi":"https://doi.org/10.1021/acs.jcim.6c00768","pmid":"https://pubmed.ncbi.nlm.nih.gov/42439482"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.6c00768","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6c00768","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/A5018100923","display_name":"Dominik Schwarz","orcid":"https://orcid.org/0000-0003-3558-8396"},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Dominik Schwarz","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5140548406","display_name":"Sven H. Giese","orcid":null},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Sven H. Giese","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5140559274","display_name":"Akansha Gupta","orcid":null},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Akansha Gupta","raw_affiliation_strings":["Broad Institute of MIT and Harvard , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Broad Institute of MIT and Harvard , , ,","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032110488","display_name":"Paulina J. Dziuba\u0144ska-Kusibab","orcid":"https://orcid.org/0000-0002-0932-3522"},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Paulina J. Dziuban\u0301ska-Kusibab","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5140160496","display_name":"Santiago D. Villalba","orcid":null},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Santiago D. Villalba","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5129424409","display_name":"Andrew Cherniack","orcid":null},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andrew Cherniack","raw_affiliation_strings":["Broad Institute of MIT and Harvard , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Broad Institute of MIT and Harvard , , ,","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5140531537","display_name":"Xiaoping Yang","orcid":null},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xiaoping Yang","raw_affiliation_strings":["Broad Institute of MIT and Harvard , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Broad Institute of MIT and Harvard , , ,","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5140517843","display_name":"David Root","orcid":null},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Root","raw_affiliation_strings":["Broad Institute of MIT and Harvard , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Broad Institute of MIT and Harvard , , ,","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001423291","display_name":"Gizem Karsli-Uzunbas","orcid":null},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gizem Karsli-Uzunbas","raw_affiliation_strings":["Broad Institute of MIT and Harvard , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Broad Institute of MIT and Harvard , , ,","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5137650204","display_name":"Heidi Greulich","orcid":"https://orcid.org/0000-0001-5571-9862"},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Heidi Greulich","raw_affiliation_strings":["Broad Institute of MIT and Harvard , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Broad Institute of MIT and Harvard , , ,","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055135489","display_name":"Franziska Siegel","orcid":null},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Franziska Siegel","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016610225","display_name":"Atanas Kamburov","orcid":"https://orcid.org/0000-0002-0580-0619"},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Atanas Kamburov","raw_affiliation_strings":["Owkin France , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Owkin France , , ,","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029670475","display_name":"Ekaterina Nevedomskaya","orcid":null},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Ekaterina Nevedomskaya","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049958324","display_name":"Clara D. Christ","orcid":"https://orcid.org/0000-0002-5424-9819"},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Clara Christ","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":"https://orcid.org/0000-0002-5424-9819","affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056535696","display_name":"Matteo Aldeghi","orcid":"https://orcid.org/0000-0003-0019-8806"},"institutions":[{"id":"https://openalex.org/I150569930","display_name":"Bayer (United States)","ror":"https://ror.org/034ffbg36","country_code":"US","type":"company","lineage":["https://openalex.org/I150569930","https://openalex.org/I67348948"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Matteo Aldeghi","raw_affiliation_strings":["Bayer Research and Innovation Center , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bayer Research and Innovation Center , , , ,","institution_ids":["https://openalex.org/I150569930"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5052721370","display_name":"J\u00e9r\u00e9mie Mortier","orcid":"https://orcid.org/0000-0001-8707-3867"},"institutions":[{"id":"https://openalex.org/I67348948","display_name":"Bayer (Germany)","ror":"https://ror.org/04hmn8g73","country_code":"DE","type":"company","lineage":["https://openalex.org/I67348948"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Je\u0301re\u0301mie Mortier","raw_affiliation_strings":["Bayer AG , , ,"],"raw_orcid":"https://orcid.org/0000-0001-8707-3867","affiliations":[{"raw_affiliation_string":"Bayer AG , , ,","institution_ids":["https://openalex.org/I67348948"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5018100923","https://openalex.org/A5052721370"],"corresponding_institution_ids":["https://openalex.org/I67348948"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.70629323,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"66","issue":"14","first_page":"8284","last_page":"8294"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.5388000011444092,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.5388000011444092,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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":0.061400000005960464,"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/T11764","display_name":"Evolution and Genetic Dynamics","score":0.060499999672174454,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/mutation","display_name":"Mutation","score":0.6191999912261963},{"id":"https://openalex.org/keywords/in-silico","display_name":"In silico","score":0.5907999873161316},{"id":"https://openalex.org/keywords/mutant","display_name":"Mutant","score":0.5357000231742859},{"id":"https://openalex.org/keywords/resistance-mutation","display_name":"Resistance mutation","score":0.5253000259399414},{"id":"https://openalex.org/keywords/population","display_name":"Population","score":0.47200000286102295},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"Drug resistance","score":0.45089998841285706},{"id":"https://openalex.org/keywords/identification","display_name":"Identification (biology)","score":0.43700000643730164},{"id":"https://openalex.org/keywords/cancer","display_name":"Cancer","score":0.3801000118255615}],"concepts":[{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.6191999912261963},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.5907999873161316},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.5357000231742859},{"id":"https://openalex.org/C182707283","wikidata":"https://www.wikidata.org/wiki/Q7315622","display_name":"Resistance mutation","level":5,"score":0.5253000259399414},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5189999938011169},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.47200000286102295},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.47049999237060547},{"id":"https://openalex.org/C114851261","wikidata":"https://www.wikidata.org/wiki/Q12147416","display_name":"Drug resistance","level":2,"score":0.45089998841285706},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.43700000643730164},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4320000112056732},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3801000118255615},{"id":"https://openalex.org/C2986374874","wikidata":"https://www.wikidata.org/wiki/Q8054","display_name":"Protein function","level":3,"score":0.3560999929904938},{"id":"https://openalex.org/C149129301","wikidata":"https://www.wikidata.org/wiki/Q3883802","display_name":"Neutral mutation","level":3,"score":0.3540000021457672},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.3479999899864197},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.33889999985694885},{"id":"https://openalex.org/C61727976","wikidata":"https://www.wikidata.org/wiki/Q751748","display_name":"Epistasis","level":3,"score":0.31540000438690186},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.28349998593330383},{"id":"https://openalex.org/C57473165","wikidata":"https://www.wikidata.org/wiki/Q7315604","display_name":"Resistance (ecology)","level":2,"score":0.2833000123500824},{"id":"https://openalex.org/C2779926675","wikidata":"https://www.wikidata.org/wiki/Q6943700","display_name":"Mutant protein","level":4,"score":0.28220000863075256},{"id":"https://openalex.org/C105951970","wikidata":"https://www.wikidata.org/wiki/Q1036748","display_name":"Loss function","level":4,"score":0.2678999900817871},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.265500009059906},{"id":"https://openalex.org/C176944494","wikidata":"https://www.wikidata.org/wiki/Q1415380","display_name":"Point mutation","level":4,"score":0.2572000026702881},{"id":"https://openalex.org/C91852762","wikidata":"https://www.wikidata.org/wiki/Q3307742","display_name":"Fitness landscape","level":3,"score":0.2524999976158142},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.25049999356269836}],"mesh":[{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","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":"D013816","descriptor_name":"Thermodynamics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D019950","descriptor_name":"Mitogen-Activated Protein Kinase 1","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D019950","descriptor_name":"Mitogen-Activated Protein Kinase 1","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D019950","descriptor_name":"Mitogen-Activated Protein Kinase 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019950","descriptor_name":"Mitogen-Activated Protein Kinase 1","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","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":"Q000737","qualifier_name":"chemistry","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.6c00768","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6c00768","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:42439482","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42439482","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":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.4682809114456177,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":30,"referenced_works":["https://openalex.org/W2060588922","https://openalex.org/W2078902726","https://openalex.org/W2096878348","https://openalex.org/W2131487381","https://openalex.org/W2145824104","https://openalex.org/W2152061559","https://openalex.org/W2154670681","https://openalex.org/W2180481128","https://openalex.org/W2205667543","https://openalex.org/W2535595233","https://openalex.org/W2608834008","https://openalex.org/W2888630510","https://openalex.org/W2903836900","https://openalex.org/W2913905751","https://openalex.org/W2951718918","https://openalex.org/W2967474035","https://openalex.org/W2967710850","https://openalex.org/W3146944767","https://openalex.org/W3179485843","https://openalex.org/W3195759335","https://openalex.org/W4224032811","https://openalex.org/W4306797783","https://openalex.org/W4319164454","https://openalex.org/W4367185716","https://openalex.org/W4385737488","https://openalex.org/W4387639561","https://openalex.org/W4398197244","https://openalex.org/W4407774286","https://openalex.org/W4408212879","https://openalex.org/W4415191455"],"related_works":[],"abstract_inverted_index":{"Abstract":[0],"Drug":[1],"resistance":[2,19,42,85,122,138,150,161,186],"is":[3,257],"a":[4,21,91,98,167,192,234],"major":[5],"challenge":[6],"in":[7,47,58,118],"cancer":[8,32],"therapy.":[9],"Cancer":[10],"cells":[11],"with":[12,55,90,127,191],"pre-existing":[13],"or":[14,66,253],"acquired":[15],"mutations":[16,43,82,187,190,202,240,249],"that":[17,83,135,177,225],"confer":[18,84],"to":[20,86,139,214,238,243],"given":[22],"drug":[23],"treatment":[24,38,54],"outgrow":[25],"the":[26,48,70,117,152,183,215,245],"susceptible":[27],"cell":[28],"population":[29],"and":[30,108,155,205,218,259],"cause":[31],"recurrence":[33],"after":[34],"an":[35,87,156,163],"initial":[36],"successful":[37],"response.":[39],"Knowledge":[40],"about":[41],"before":[44],"they":[45,209],"occur":[46],"clinic":[49],"could":[50,115,232],"prevent":[51],"unnecessary":[52],"patient":[53],"ineffective":[56],"drugs,":[57],"clinical":[59,64],"trials":[60],"as":[61,63,203],"well":[62],"practice,":[65],"potentially":[67,207],"speed":[68],"up":[69],"development":[71],"of":[72,100,121,162,185,248],"follow-up":[73],"compounds.":[74],"Here,":[75],"we":[76],"focused":[77],"on":[78,250],"on-target":[79],"amino":[80,141],"acid":[81,142],"inhibitor":[88,153,171],"compound":[89],"known":[92],"binding":[93],"mode.":[94],"We":[95],"evaluated":[96],"whether":[97],"combination":[99],"physics-based":[101],"free":[102],"energy":[103],"perturbation":[104],"(FEP)":[105],"affinity":[106],"estimates":[107,114,180,231],"protein":[109,112,178,226,229,254],"language":[110,227],"model-based":[111,228],"fitness":[113,179,230],"improve":[116],"silico":[119],"identification":[120,184],"mutations.":[123,143],"Validation":[124],"was":[125],"done":[126],"data":[128,146,158],"from":[129],"deep":[130],"mutational":[131],"scanning":[132],"(DMS)":[133],"experiments":[134],"tested":[136],"for":[137],"single":[140],"A":[144],"public":[145],"set":[147,159],"testing":[148,160],"ERK2":[149],"against":[151,166],"SCH772984":[154],"internal":[157],"EGFR_exon20":[164],"mutant":[165],"Bayer":[168],"small":[169],"molecule":[170],"were":[172,210],"used.":[173],"Our":[174],"results":[175],"show":[176],"can":[181],"facilitate":[182],"by":[188],"filtering":[189],"low":[193],"estimated":[194],"fitness.":[195],"Even":[196],"though":[197],"FEP":[198],"has":[199],"flagged":[200],"such":[201],"affinity-decreasing":[204],"thus":[206],"resistant,":[208],"not":[211],"resistant":[212],"according":[213],"DMS":[216],"experiment":[217],"therefore":[219],"correctly":[220],"filtered":[221],"out.":[222],"This":[223],"indicates":[224],"be":[233],"computationally":[235,260],"efficient":[236],"method":[237],"filter":[239],"without":[241],"having":[242],"model":[244],"negative":[246],"impact":[247],"native":[251],"function":[252],"stability,":[255],"which":[256],"error-prone":[258],"expensive.":[261]},"counts_by_year":[],"updated_date":"2026-08-21T09:56:20.448147","created_date":"2026-07-14T00:00:00"}