{"id":"https://openalex.org/W7214616546","doi":"https://doi.org/10.3390/ijms27209057","title":"Matched Analogue Analysis of Structural Responses Before and After Covalent Bond Formation in Wild-Type and A775_G776insYVMA HER2","display_name":"Matched Analogue Analysis of Structural Responses Before and After Covalent Bond Formation in Wild-Type and A775_G776insYVMA HER2","publication_year":2026,"publication_date":"2026-10-13","ids":{"openalex":"https://openalex.org/W7214616546","doi":"https://doi.org/10.3390/ijms27209057","pmid":"https://pubmed.ncbi.nlm.nih.gov/42941830","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13705266"},"language":"en","primary_location":{"id":"doi:10.3390/ijms27209057","doi":"https://doi.org/10.3390/ijms27209057","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms27209057","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/ijms27209057","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5003022683","display_name":"Keke Fan","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Keke Fan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Yanan Xu","orcid":"https://orcid.org/0009-0002-7998-0808","observed_orcids":["https://orcid.org/0009-0002-7998-0808"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yanan Xu","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0009-0002-7998-0808","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5153254645","display_name":"Qiwei Ye","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Qiwei Ye","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5041782163","display_name":"Mingliang Zeng","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mingliang Zeng","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5153308086","display_name":"Hongwang Xiao","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Hongwang Xiao","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081319198","display_name":"Shanyan Mo","orcid":"https://orcid.org/0000-0002-1601-0057","observed_orcids":["https://orcid.org/0000-0002-1601-0057"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shanyan Mo","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-1601-0057","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5153215297","display_name":"Sha Hu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Sha Hu","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5152980019","display_name":"Liming Hu","orcid":"https://orcid.org/0000-0001-6021-0462","observed_orcids":["https://orcid.org/0000-0001-6021-0462"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Liming Hu","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-6021-0462","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5152980019","https://openalex.org/A5153215297"],"corresponding_institution_ids":[],"apc_list":{"value":2900,"currency":"CHF","value_usd":3499},"apc_paid":{"value":2900,"currency":"CHF","value_usd":3499},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.69196479,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"27","issue":"20","first_page":"9057","last_page":"9057"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.4787999987602234,"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":0.4787999987602234,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.2590000033378601,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.0681999996304512,"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/her2","display_name":"HER2","score":0.9350000023841858},{"id":"https://openalex.org/keywords/irreversible-kinase-inhibitors","display_name":"irreversible kinase inhibitors","score":0.7379999756813049},{"id":"https://openalex.org/keywords/covalent-bond-formation","display_name":"covalent bond formation","score":0.7749999761581421},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.7919999957084656},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"molecular dynamics","score":0.5289999842643738},{"id":"https://openalex.org/keywords/covalent-adducts","display_name":"covalent adducts","score":0.7710000276565552},{"id":"https://openalex.org/keywords/michael-addition","display_name":"Michael addition","score":0.6769999861717224},{"id":"https://openalex.org/keywords/cyclization","display_name":"cyclization","score":0.4320000112056732},{"id":"https://openalex.org/keywords/structural-descriptors","display_name":"structural descriptors","score":0.3370000123977661}],"concepts":[{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.7799000144004822},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7470999956130981},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.5807999968528748},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.4602999985218048},{"id":"https://openalex.org/C148898269","wikidata":"https://www.wikidata.org/wiki/Q1108792","display_name":"Kinetics","level":2,"score":0.4474000036716461},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.40549999475479126},{"id":"https://openalex.org/C149629883","wikidata":"https://www.wikidata.org/wiki/Q660926","display_name":"Fraction (chemistry)","level":2,"score":0.3495999872684479},{"id":"https://openalex.org/C143724316","wikidata":"https://www.wikidata.org/wiki/Q312468","display_name":"Series (stratigraphy)","level":2,"score":0.34279999136924744},{"id":"https://openalex.org/C49271019","wikidata":"https://www.wikidata.org/wiki/Q1969120","display_name":"Structural change","level":2,"score":0.3366999924182892},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.3287999927997589},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.3188999891281128},{"id":"https://openalex.org/C57992300","wikidata":"https://www.wikidata.org/wiki/Q2066956","display_name":"Potency","level":3,"score":0.3082999885082245},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.2874000072479248},{"id":"https://openalex.org/C193042331","wikidata":"https://www.wikidata.org/wiki/Q1772003","display_name":"Structure\u2013activity relationship","level":3,"score":0.266400009393692},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.26179999113082886},{"id":"https://openalex.org/C112313634","wikidata":"https://www.wikidata.org/wiki/Q7886648","display_name":"Complement (music)","level":5,"score":0.2549000084400177}],"mesh":[{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018719","descriptor_name":"Erb-b2 Receptor Tyrosine Kinases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D018719","descriptor_name":"Erb-b2 Receptor Tyrosine Kinases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D018719","descriptor_name":"Erb-b2 Receptor Tyrosine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D018719","descriptor_name":"Erb-b2 Receptor Tyrosine Kinases","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":true},{"descriptor_ui":"D047428","descriptor_name":"Protein Kinase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.3390/ijms27209057","doi":"https://doi.org/10.3390/ijms27209057","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms27209057","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},{"id":"doi:10.20944/preprints202609.2230.v1","doi":"https://doi.org/10.20944/preprints202609.2230.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202609.2230.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},{"id":"pmh:oai:pubmedcentral.nih.gov:13705266","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13705266/","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13705266/pdf/ijms-27-09057.pdf","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":"Int J Mol Sci","raw_type":"Text"},{"id":"pmid:42941830","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42941830","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,"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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International journal of molecular sciences","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.3390/ijms27209057","doi":"https://doi.org/10.3390/ijms27209057","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms27209057","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.4043000042438507}],"study_designs":[],"awards":[{"id":"https://openalex.org/G9001172536","display_name":null,"funder_award_id":"Z20250390","funder_id":"https://openalex.org/F4320323068","funder_display_name":"Beijing Postdoctoral Science Foundation"},{"id":"https://openalex.org/G9001174850","display_name":null,"funder_award_id":"7232243","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"}],"funders":[{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320323068","display_name":"Beijing Postdoctoral Science Foundation","ror":"https://ror.org/0426zh255"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7214616546.pdf","grobid_xml":"https://content.openalex.org/works/W7214616546.grobid-xml"},"referenced_works_count":43,"referenced_works":["https://openalex.org/W1968427979","https://openalex.org/W2000390423","https://openalex.org/W2010993054","https://openalex.org/W2014678042","https://openalex.org/W2036160927","https://openalex.org/W2045694062","https://openalex.org/W2049449785","https://openalex.org/W2068171522","https://openalex.org/W2082592896","https://openalex.org/W2087952495","https://openalex.org/W2131964519","https://openalex.org/W2138863392","https://openalex.org/W2153228625","https://openalex.org/W2317488620","https://openalex.org/W2335178031","https://openalex.org/W2401258374","https://openalex.org/W2527718275","https://openalex.org/W2562677145","https://openalex.org/W2785841326","https://openalex.org/W2801651204","https://openalex.org/W2806290811","https://openalex.org/W2893411741","https://openalex.org/W2904506792","https://openalex.org/W2918370785","https://openalex.org/W3004785694","https://openalex.org/W3013682926","https://openalex.org/W3087625458","https://openalex.org/W3167019654","https://openalex.org/W3195811056","https://openalex.org/W3200238080","https://openalex.org/W3206696710","https://openalex.org/W4200153374","https://openalex.org/W4211090364","https://openalex.org/W4281480567","https://openalex.org/W4281670905","https://openalex.org/W4288069830","https://openalex.org/W4293084539","https://openalex.org/W4362523142","https://openalex.org/W4387729019","https://openalex.org/W4393097527","https://openalex.org/W4399203603","https://openalex.org/W4411022988","https://openalex.org/W7212252726"],"related_works":["https://openalex.org/W3087625458","https://openalex.org/W7126143510","https://openalex.org/W4413105359","https://openalex.org/W3174425309","https://openalex.org/W3093091145","https://openalex.org/W2996077653","https://openalex.org/W4409841385","https://openalex.org/W3086340541","https://openalex.org/W2897074743","https://openalex.org/W2097817246"],"abstract_inverted_index":{"Endpoint":[0],"structure\u2013activity":[1],"relationships":[2],"(SAR)":[3],"for":[4],"irreversible":[5,38],"inhibitors":[6,39],"can":[7],"integrate":[8],"reversible":[9],"binding,":[10],"covalent":[11,97],"chemistry,":[12],"conformational":[13],"behavior,":[14],"and":[15,44,99,161,207,217],"cellular":[16,175],"factors,":[17],"making":[18],"it":[19,138,190],"difficult":[20],"to":[21,26,67,92,105,122,134,143,169,225],"assign":[22],"a":[23,27,33,74,172,249],"potency":[24,235],"change":[25],"single":[28,230],"molecular":[29,61],"event.":[30],"We":[31],"reanalyzed":[32],"previously":[34],"reported":[35],"series":[36,187],"of":[37,40,71,119,174,197,251],"wild-type":[41],"(WT)":[42],"HER2":[43,45,215],"A775_G776insYVMA":[46],"(HER2YVMA)":[47],"as":[48],"six":[49,151,238],"matched":[50],"analogue":[51],"pairs.":[52,239],"Three":[53],"complementary":[54],"analyses":[55,241],"were":[56,65,90,103,223],"kept":[57],"physically":[58],"distinct.":[59],"Pre-reaction":[60],"dynamics":[62],"(MD)":[63],"trajectories":[64,102],"used":[66,91,104],"quantify":[68],"the":[69,126,146,156,164,185,192,203,208,226],"fraction":[70,129,166,183],"frames":[72],"satisfying":[73],"predefined":[75,204],"near-attack-conformation":[76],"(NAC)-like":[77],"distance\u2013angle":[78],"criterion;":[79],"continuous":[80],"structural":[81,94,205,231],"descriptors":[82],"calculated":[83],"from":[84,132,141,167],"OC2-generated":[85,198],"covalently":[86,199],"linked":[87,200],"HER2\u2013inhibitor":[88],"structures":[89,201],"characterize":[93,106],"differences":[95],"after":[96],"linkage;":[98],"covalent-adduct":[100],"MD":[101,210],"post-bond-formation":[107],"dynamics.":[108],"The":[109,177,195],"Michael-addition":[110],"step":[111],"itself":[112],"was":[113],"neither":[114],"simulated":[115],"nor":[116],"measured.":[117],"Cyclization":[118],"compound":[120,123],"3":[121],"9c":[124],"increased":[125,163,181],"NAC-like":[127,165],"frame":[128],"in":[130,139,184,191],"HER2WT":[131],"0.0217%":[133],"0.358%":[135],"but":[136,188,245],"decreased":[137],"HER2YVMA":[140],"0.745%":[142],"0.333%,":[144],"with":[145,214],"direction":[147],"preserved":[148],"across":[149,202,236],"all":[150,237],"sensitivity":[152],"definitions.":[153],"In":[154],"HER2YVMA,":[155],"modification":[157,180],"distinguishing":[158],"compounds":[159],"4a":[160],"5a":[162],"2.620%":[168],"6.244%":[170],"despite":[171],"loss":[173],"potency.":[176],"analogous":[178],"tail":[179],"this":[182],"8c/10e":[186],"reduced":[189],"9c/11f":[193],"series.":[194],"distribution":[196],"coordinate":[206,227],"final-adduct":[209],"readouts":[211],"likewise":[212],"varied":[213],"context":[216],"scaffold,":[218],"although":[219],"some":[220],"differential":[221],"effects":[222],"sensitive":[224],"reference.":[228],"No":[229],"readout":[232],"tracked":[233],"endpoint":[234],"These":[240],"complement":[242],"experimental":[243],"SAR":[244],"do":[246],"not":[247],"provide":[248],"measure":[250],"reaction":[252],"kinetics":[253],"or":[254],"thermodynamic":[255],"populations.":[256]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-29T00:00:00"}