{"id":"https://openalex.org/W7123364419","doi":"https://doi.org/10.1021/acs.jcim.5c01098","title":"Enhancing CYP450-Ligand Binding Predictions: A Comparative Analysis of Ligand-Based and Hybrid Machine Learning Models","display_name":"Enhancing CYP450-Ligand Binding Predictions: A Comparative Analysis of Ligand-Based and Hybrid Machine Learning Models","publication_year":2026,"publication_date":"2026-01-13","ids":{"openalex":"https://openalex.org/W7123364419","doi":"https://doi.org/10.1021/acs.jcim.5c01098","pmid":"https://pubmed.ncbi.nlm.nih.gov/41527345"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c01098","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01098","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/A5122866248","display_name":"Anastasiia Tikhonova","orcid":null},"institutions":[{"id":"https://openalex.org/I115228651","display_name":"Agency for Science, Technology and Research","ror":"https://ror.org/036wvzt09","country_code":"SG","type":"government","lineage":["https://openalex.org/I115228651"]},{"id":"https://openalex.org/I165932596","display_name":"National University of Singapore","ror":"https://ror.org/01tgyzw49","country_code":"SG","type":"education","lineage":["https://openalex.org/I165932596"]},{"id":"https://openalex.org/I4210148498","display_name":"Bioinformatics Institute","ror":"https://ror.org/044w3nw43","country_code":"SG","type":"facility","lineage":["https://openalex.org/I115228651","https://openalex.org/I2801752549","https://openalex.org/I4210148498"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Anastasiia Tikhonova","raw_affiliation_strings":["Agency for Science, Technology and Research (A*STAR)","Bioinformatics Institute (BII)","Department of Pharmacy and Pharmaceutical Sciences","National University of Singapore"],"raw_orcid":"https://orcid.org/0009-0008-5803-703X","affiliations":[{"raw_affiliation_string":"Agency for Science, Technology and Research (A*STAR)","institution_ids":["https://openalex.org/I115228651"]},{"raw_affiliation_string":"Bioinformatics Institute (BII)","institution_ids":["https://openalex.org/I4210148498"]},{"raw_affiliation_string":"Department of Pharmacy and Pharmaceutical Sciences","institution_ids":[]},{"raw_affiliation_string":"National University of Singapore","institution_ids":["https://openalex.org/I165932596"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070406461","display_name":"E Chan","orcid":null},"institutions":[{"id":"https://openalex.org/I165932596","display_name":"National University of Singapore","ror":"https://ror.org/01tgyzw49","country_code":"SG","type":"education","lineage":["https://openalex.org/I165932596"]}],"countries":["SG"],"is_corresponding":false,"raw_author_name":"Eric Chun Yong Chan","raw_affiliation_strings":["Department of Pharmacy and Pharmaceutical Sciences","National University of Singapore"],"raw_orcid":"https://orcid.org/0000-0001-6107-9072","affiliations":[{"raw_affiliation_string":"Department of Pharmacy and Pharmaceutical Sciences","institution_ids":[]},{"raw_affiliation_string":"National University of Singapore","institution_ids":["https://openalex.org/I165932596"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5122880866","display_name":"Hao Fan","orcid":null},"institutions":[{"id":"https://openalex.org/I115228651","display_name":"Agency for Science, Technology and Research","ror":"https://ror.org/036wvzt09","country_code":"SG","type":"government","lineage":["https://openalex.org/I115228651"]},{"id":"https://openalex.org/I144648050","display_name":"Yong In University","ror":"https://ror.org/035qaq447","country_code":"KR","type":"education","lineage":["https://openalex.org/I144648050"]},{"id":"https://openalex.org/I165932596","display_name":"National University of Singapore","ror":"https://ror.org/01tgyzw49","country_code":"SG","type":"education","lineage":["https://openalex.org/I165932596"]},{"id":"https://openalex.org/I4210126319","display_name":"Duke-NUS Medical School","ror":"https://ror.org/02j1m6098","country_code":"SG","type":"education","lineage":["https://openalex.org/I165932596","https://openalex.org/I170897317","https://openalex.org/I4210126319"]},{"id":"https://openalex.org/I4210146172","display_name":"Cellular Therapeutics (United Kingdom)","ror":"https://ror.org/04ea9m912","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210146172"]},{"id":"https://openalex.org/I4210148498","display_name":"Bioinformatics Institute","ror":"https://ror.org/044w3nw43","country_code":"SG","type":"facility","lineage":["https://openalex.org/I115228651","https://openalex.org/I2801752549","https://openalex.org/I4210148498"]}],"countries":["GB","KR","SG"],"is_corresponding":true,"raw_author_name":"Hao Fan","raw_affiliation_strings":["Agency for Science, Technology and Research (A*STAR)","Bioinformatics Institute (BII)","Cancer and Stem Cell Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Republic of Singapore","Chinese Institutes for Medical Research","Department of Biochemistry, Yong Loo Lin School of Medicine","Institute for Molecular and Cellular Therapeutics","National University of Singapore","Synthetic Biology Translational Research Program, Yong Loo Lin School of Medicine"],"raw_orcid":"https://orcid.org/0000-0003-0199-9752","affiliations":[{"raw_affiliation_string":"Agency for Science, Technology and Research (A*STAR)","institution_ids":["https://openalex.org/I115228651"]},{"raw_affiliation_string":"Bioinformatics Institute (BII)","institution_ids":["https://openalex.org/I4210148498"]},{"raw_affiliation_string":"Cancer and Stem Cell Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Republic of Singapore","institution_ids":["https://openalex.org/I4210126319"]},{"raw_affiliation_string":"Chinese Institutes for Medical Research","institution_ids":[]},{"raw_affiliation_string":"Department of Biochemistry, Yong Loo Lin School of Medicine","institution_ids":["https://openalex.org/I144648050"]},{"raw_affiliation_string":"Institute for Molecular and Cellular Therapeutics","institution_ids":["https://openalex.org/I4210146172"]},{"raw_affiliation_string":"National University of Singapore","institution_ids":["https://openalex.org/I165932596"]},{"raw_affiliation_string":"Synthetic Biology Translational Research Program, Yong Loo Lin School of Medicine","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5122880866"],"corresponding_institution_ids":["https://openalex.org/I115228651","https://openalex.org/I144648050","https://openalex.org/I165932596","https://openalex.org/I4210126319","https://openalex.org/I4210146172","https://openalex.org/I4210148498"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.10104708,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"66","issue":"2","first_page":"834","last_page":"846"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.8906999826431274,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.8906999826431274,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.06469999998807907,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"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/T12254","display_name":"Machine Learning in Bioinformatics","score":0.01720000058412552,"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/drug-discovery","display_name":"Drug discovery","score":0.5203999876976013},{"id":"https://openalex.org/keywords/docking","display_name":"Docking (animal)","score":0.4625000059604645},{"id":"https://openalex.org/keywords/benchmarking","display_name":"Benchmarking","score":0.4616999924182892},{"id":"https://openalex.org/keywords/function","display_name":"Function (biology)","score":0.35839998722076416},{"id":"https://openalex.org/keywords/ranking","display_name":"Ranking (information retrieval)","score":0.3562999963760376},{"id":"https://openalex.org/keywords/quantitative-structure\u2013activity-relationship","display_name":"Quantitative structure\u2013activity relationship","score":0.3334999978542328}],"concepts":[{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.6766999959945679},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.6758000254631042},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.5874999761581421},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5203999876976013},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.4625000059604645},{"id":"https://openalex.org/C86251818","wikidata":"https://www.wikidata.org/wiki/Q816754","display_name":"Benchmarking","level":2,"score":0.4616999924182892},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.35839998722076416},{"id":"https://openalex.org/C189430467","wikidata":"https://www.wikidata.org/wiki/Q7293293","display_name":"Ranking (information retrieval)","level":2,"score":0.3562999963760376},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3411000072956085},{"id":"https://openalex.org/C164126121","wikidata":"https://www.wikidata.org/wiki/Q766383","display_name":"Quantitative structure\u2013activity relationship","level":2,"score":0.3334999978542328},{"id":"https://openalex.org/C51632099","wikidata":"https://www.wikidata.org/wiki/Q3985153","display_name":"Training set","level":2,"score":0.3319000005722046},{"id":"https://openalex.org/C68762167","wikidata":"https://www.wikidata.org/wiki/Q910164","display_name":"Cheminformatics","level":2,"score":0.30000001192092896},{"id":"https://openalex.org/C124101348","wikidata":"https://www.wikidata.org/wiki/Q172491","display_name":"Data mining","level":1,"score":0.2912999987602234},{"id":"https://openalex.org/C103697762","wikidata":"https://www.wikidata.org/wiki/Q4112105","display_name":"Virtual screening","level":3,"score":0.2904999852180481},{"id":"https://openalex.org/C66024118","wikidata":"https://www.wikidata.org/wiki/Q1122506","display_name":"Computational model","level":2,"score":0.2854999899864197},{"id":"https://openalex.org/C2989108626","wikidata":"https://www.wikidata.org/wiki/Q904407","display_name":"Drug target","level":2,"score":0.2587999999523163}],"mesh":[{"descriptor_ui":"D000069550","descriptor_name":"Machine Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000069550","descriptor_name":"Machine Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D003577","descriptor_name":"Cytochrome P-450 Enzyme System","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D003577","descriptor_name":"Cytochrome P-450 Enzyme System","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D003577","descriptor_name":"Cytochrome P-450 Enzyme System","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D003577","descriptor_name":"Cytochrome P-450 Enzyme System","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D062105","descriptor_name":"Molecular Docking Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5c01098","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01098","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:41527345","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41527345","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":[],"funders":[{"id":"https://openalex.org/F4320320696","display_name":"Agency for Science, Technology and Research","ror":"https://ror.org/036wvzt09"},{"id":"https://openalex.org/F4320334741","display_name":"Bioinformatics Institute","ror":"https://ror.org/044w3nw43"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":27,"referenced_works":["https://openalex.org/W1835740130","https://openalex.org/W1971007618","https://openalex.org/W1985588649","https://openalex.org/W1989405983","https://openalex.org/W1996903743","https://openalex.org/W1997172276","https://openalex.org/W2017417437","https://openalex.org/W2044834685","https://openalex.org/W2058835307","https://openalex.org/W2069457036","https://openalex.org/W2073021822","https://openalex.org/W2087955696","https://openalex.org/W2108243628","https://openalex.org/W2115763439","https://openalex.org/W2130479394","https://openalex.org/W2143482176","https://openalex.org/W2209144082","https://openalex.org/W2593436234","https://openalex.org/W2622236128","https://openalex.org/W2883054842","https://openalex.org/W3060135982","https://openalex.org/W3084823836","https://openalex.org/W3198581111","https://openalex.org/W4211247432","https://openalex.org/W4383216583","https://openalex.org/W4387564442","https://openalex.org/W4393936599"],"related_works":[],"abstract_inverted_index":{"Predicting":[0],"cytochrome":[1],"P450":[2],"(CYP450)":[3],"ligand":[4,71],"binding":[5,130,145],"is":[6],"critical":[7],"in":[8,107,129],"early-stage":[9],"drug":[10,17,148],"discovery":[11],"as":[12],"CYP450-mediated":[13],"metabolism":[14],"profoundly":[15],"influences":[16],"efficacy,":[18],"safety,":[19],"and":[20,32,75,90,98,114,123],"adverse":[21],"reaction":[22],"risks.":[23],"However,":[24],"experimental":[25],"determination":[26],"of":[27],"CYP450-ligand":[28],"interactions":[29],"remains":[30],"resource-":[31],"time-intensive,":[33],"underscoring":[34],"the":[35],"need":[36],"for":[37,53,138],"robust":[38],"computational":[39,140],"alternatives.":[40],"While":[41],"ligand-based":[42,115],"methods":[43],"are":[44],"commonly":[45],"employed,":[46],"they":[47],"often":[48],"fail":[49],"to":[50,142],"fully":[51],"account":[52],"structural":[54,91],"intricacies":[55],"governing":[56],"protein-ligand":[57,76],"interactions.":[58],"To":[59],"address":[60],"this":[61],"gap,":[62],"we":[63],"developed":[64],"a":[65,135],"hybrid":[66],"machine":[67],"learning":[68],"framework":[69,137],"integrating":[70],"descriptors,":[72,74],"protein":[73],"interaction":[77,92],"descriptors":[78],"that":[79],"include":[80],"molecular":[81,112],"docking-derived":[82],"parameters,":[83],"rescoring":[84],"function":[85],"components":[86],"from":[87],"multiple":[88],"algorithms,":[89],"fingerprints":[93],"(SIFt).":[94],"Evaluated":[95],"on":[96],"CYP1A2":[97],"CYP17A1":[99],"isoforms,":[100],"our":[101],"model":[102],"demonstrated":[103],"superior":[104],"predictive":[105],"accuracy":[106],"cross-validation":[108],"compared":[109],"with":[110],"stand-alone":[111],"docking":[113],"approaches.":[116],"Furthermore,":[117],"benchmarking":[118],"against":[119],"state-of-the-art":[120],"tools":[121,141],"(SwissADME":[122],"ADMETlab":[124],"3.0)":[125],"revealed":[126],"enhanced":[127],"performance":[128],"prediction.":[131],"This":[132],"work":[133],"establishes":[134],"versatile":[136],"advancing":[139],"prioritize":[143],"CYP450":[144],"assessments":[146],"during":[147],"discovery.":[149]},"counts_by_year":[],"updated_date":"2026-03-27T05:58:40.876381","created_date":"2026-01-14T00:00:00"}