{"id":"https://openalex.org/W7220359591","doi":"https://doi.org/10.26434/chemrxiv.15009874/v1","title":"Resolving Kinase Resistance Landscapes via Antisymmetric Siamese Graph Networks and Co-Folding Ensembles","display_name":"Resolving Kinase Resistance Landscapes via Antisymmetric Siamese Graph Networks and Co-Folding Ensembles","publication_year":2026,"publication_date":"2026-10-05","ids":{"openalex":"https://openalex.org/W7220359591","doi":"https://doi.org/10.26434/chemrxiv.15009874/v1"},"language":"en","primary_location":{"id":"doi:10.26434/chemrxiv.15009874/v1","doi":"https://doi.org/10.26434/chemrxiv.15009874/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15009874/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009874/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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":"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"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009874/v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5157559176","display_name":"Sharif Ahmad Naikoo","orcid":"https://orcid.org/0000-0002-7792-9278","observed_orcids":["https://orcid.org/0000-0002-7792-9278"]},"institutions":[{"id":"https://openalex.org/I94234084","display_name":"Indian Institute of Technology Kanpur","ror":"https://ror.org/05pjsgx75","country_code":"IN","type":"education","lineage":["https://openalex.org/I94234084"]}],"countries":["IN"],"is_corresponding":true,"raw_author_name":"Sharif Ahmad Naikoo","raw_affiliation_strings":["Department of Chemistry, Indian Institute of Technology Kanpur India, Kalyanpur, Kanpur, Uttar Pradesh, India, 208016"],"raw_orcid":"https://orcid.org/0000-0002-7792-9278","affiliations":[{"raw_affiliation_string":"Department of Chemistry, Indian Institute of Technology Kanpur India, Kalyanpur, Kanpur, Uttar Pradesh, India, 208016","institution_ids":["https://openalex.org/I94234084"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5157559176"],"corresponding_institution_ids":["https://openalex.org/I94234084"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9955999851226807,"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"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9955999851226807,"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.00139999995008111,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.0013000000035390258,"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/kinase-inhibitor-resistance","display_name":"kinase inhibitor resistance","score":0.9390000104904175},{"id":"https://openalex.org/keywords/conformational-ensembles","display_name":"conformational ensembles","score":0.796999990940094},{"id":"https://openalex.org/keywords/free-energy-calculations","display_name":"free energy calculation","score":0.5130000114440918},{"id":"https://openalex.org/keywords/egfr-c797s","display_name":"EGFR C797S","score":0.968999981880188},{"id":"https://openalex.org/keywords/ponatinib","display_name":"ponatinib","score":0.8679999709129333},{"id":"https://openalex.org/keywords/osimertinib","display_name":"osimertinib","score":0.9980000257492065},{"id":"https://openalex.org/keywords/precision-oncology","display_name":"precision oncology","score":0.6669999957084656},{"id":"https://openalex.org/keywords/drug-resistance-prediction","display_name":"drug resistance prediction","score":0.3149999976158142}],"concepts":[{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5623000264167786},{"id":"https://openalex.org/C132525143","wikidata":"https://www.wikidata.org/wiki/Q141488","display_name":"Graph","level":2,"score":0.46070000529289246},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4253000020980835},{"id":"https://openalex.org/C114825156","wikidata":"https://www.wikidata.org/wiki/Q4775328","display_name":"Antisymmetry","level":2,"score":0.41819998621940613},{"id":"https://openalex.org/C80444323","wikidata":"https://www.wikidata.org/wiki/Q2878974","display_name":"Theoretical computer science","level":1,"score":0.40959998965263367},{"id":"https://openalex.org/C2780381907","wikidata":"https://www.wikidata.org/wiki/Q198728","display_name":"Ponatinib","level":5,"score":0.38119998574256897},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.37619999051094055},{"id":"https://openalex.org/C197657726","wikidata":"https://www.wikidata.org/wiki/Q174733","display_name":"Bipartite graph","level":3,"score":0.3391999900341034},{"id":"https://openalex.org/C54732982","wikidata":"https://www.wikidata.org/wiki/Q1415345","display_name":"Modulo","level":2,"score":0.33309999108314514},{"id":"https://openalex.org/C98763669","wikidata":"https://www.wikidata.org/wiki/Q176645","display_name":"Markov chain","level":2,"score":0.32739999890327454},{"id":"https://openalex.org/C2781067378","wikidata":"https://www.wikidata.org/wiki/Q17027399","display_name":"Interpretability","level":2,"score":0.2921999990940094},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.2732999920845032},{"id":"https://openalex.org/C182707283","wikidata":"https://www.wikidata.org/wiki/Q7315622","display_name":"Resistance mutation","level":5,"score":0.27059999108314514},{"id":"https://openalex.org/C201194858","wikidata":"https://www.wikidata.org/wiki/Q898238","display_name":"Steric effects","level":2,"score":0.26930001378059387},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.2680000066757202},{"id":"https://openalex.org/C43711488","wikidata":"https://www.wikidata.org/wiki/Q7534783","display_name":"Skew","level":2,"score":0.26409998536109924},{"id":"https://openalex.org/C10679952","wikidata":"https://www.wikidata.org/wiki/Q5308937","display_name":"Druggability","level":3,"score":0.26190000772476196},{"id":"https://openalex.org/C2777044963","wikidata":"https://www.wikidata.org/wiki/Q5384707","display_name":"Equivalence class (music)","level":2,"score":0.2587999999523163},{"id":"https://openalex.org/C199422724","wikidata":"https://www.wikidata.org/wiki/Q41118","display_name":"Quotient","level":2,"score":0.2540999948978424},{"id":"https://openalex.org/C79337645","wikidata":"https://www.wikidata.org/wiki/Q779824","display_name":"Outlier","level":2,"score":0.25049999356269836},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.25029999017715454}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.26434/chemrxiv.15009874/v1","doi":"https://doi.org/10.26434/chemrxiv.15009874/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15009874/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009874/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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":"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"}],"best_oa_location":{"id":"doi:10.26434/chemrxiv.15009874/v1","doi":"https://doi.org/10.26434/chemrxiv.15009874/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15009874/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009874/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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":"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"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320320712","display_name":"Indian Institute of Technology Kanpur","ror":"https://ror.org/05pjsgx75"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7220359591.pdf","grobid_xml":"https://content.openalex.org/works/W7220359591.grobid-xml"},"referenced_works_count":1,"referenced_works":["https://openalex.org/W2918342466"],"related_works":["https://openalex.org/W4407774286","https://openalex.org/W4408212879","https://openalex.org/W2798338906","https://openalex.org/W4396964970","https://openalex.org/W7162473423","https://openalex.org/W6958508897","https://openalex.org/W7128158261","https://openalex.org/W4391658376","https://openalex.org/W7205000436","https://openalex.org/W4416947324"],"abstract_inverted_index":{"Acquired":[0],"clinical":[1,140],"resistance":[2,109,148],"to":[3],"small-molecule":[4],"kinase":[5,108],"inhibitors":[6],"arising":[7],"from":[8],"single-point":[9],"mutations":[10],"within":[11],"the":[12,64,111,143,151,155,164],"ATP-binding":[13],"cleft":[14],"presents":[15],"a":[16,71,135],"critical":[17],"challenge":[18],"in":[19],"precision":[20],"oncology.":[21],"Conventional":[22],"computational":[23,56],"modeling":[24],"relies":[25],"either":[26],"on":[27,105],"rigid":[28],"docking\u2014which":[29],"overlooks":[30],"induced":[31],"structural":[32],"alterations\u2014or":[33],"computationally":[34],"demanding":[35],"alchemical":[36],"free":[37],"energy":[38],"perturbation":[39],"(FEP)":[40],"methods":[41],"that":[42,87],"cannot":[43],"scale":[44],"across":[45],"wide":[46],"mutational":[47],"panels.":[48],"In":[49],"this":[50],"work,":[51],"we":[52,80],"present":[53],"an":[54,82,114],"end-to-end":[55],"methodology":[57],"integrating":[58],"multi-state":[59],"conformational":[60],"ensemble":[61],"generation":[62],"via":[63],"generative":[65],"biomolecular":[66],"co-folding":[67],"engine":[68],"Boltz":[69],"with":[70],"continuous":[72],"distance-aware":[73],"Siamese":[74],"Graph":[75],"Neural":[76],"Network":[77],"(GNN).":[78],"Crucially,":[79],"introduce":[81],"unconstrained":[83],"bias-free":[84],"difference":[85],"head":[86],"strictly":[88],"enforces":[89],"thermodynamic":[90],"antisymmetry":[91],"(f":[92],"(0)":[93],"\u2261":[94],"0.0":[95],"kcal/mol),":[96],"eliminating":[97],"trivial":[98],"baseline":[99],"drift.":[100],"Under":[101],"rigorous":[102],"5-fold":[103],"cross-validation":[104],"experimentally":[106],"characterized":[107],"pairs,":[110],"model":[112],"achieves":[113],"out-of-fold":[115],"root-mean-square":[116],"error":[117],"(RMSE)":[118],"of":[119,138,154,167],"1.637":[120],"kcal/mol":[121],"(MAE":[122],"=":[123,128,132],"1.459":[124],"kcal/mol,":[125],"Pearson":[126],"R":[127],"0.239,":[129],"Spearman":[130],"\u03c1":[131],"0.260).":[133],"Across":[134],"prospective":[136],"panel":[137],"52":[139],"kinase-inhibitor":[141],"complexes,":[142],"architecture":[144],"structurally":[145],"rationalizes":[146],"key":[147],"patterns,":[149],"resolving":[150],"steric":[152],"disruption":[153],"ABL1":[156],"T315I":[157],"gatekeeper":[158],"mutation":[159],"circumvented":[160],"by":[161],"ponatinib":[162],"and":[163],"covalent":[165],"ablation":[166],"EGFR":[168],"C797S":[169],"against":[170],"osimertinib.":[171]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-10-06T00:00:00"}
