{"id":"https://openalex.org/W4413290802","doi":"https://doi.org/10.1021/acs.jcim.5c00921","title":"AI-Designed Molecules in Drug Discovery, Structural Novelty Evaluation, and Implications","display_name":"AI-Designed Molecules in Drug Discovery, Structural Novelty Evaluation, and Implications","publication_year":2025,"publication_date":"2025-08-18","ids":{"openalex":"https://openalex.org/W4413290802","doi":"https://doi.org/10.1021/acs.jcim.5c00921","pmid":"https://pubmed.ncbi.nlm.nih.gov/40820734"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c00921","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00921","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":"review","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/A5107829160","display_name":"S. Xie","orcid":null},"institutions":[{"id":"https://openalex.org/I4210086405","display_name":"National Institute of Biological Sciences, Beijing","ror":"https://ror.org/00wksha49","country_code":"CN","type":"facility","lineage":["https://openalex.org/I4210086405"]},{"id":"https://openalex.org/I99065089","display_name":"Tsinghua University","ror":"https://ror.org/03cve4549","country_code":"CN","type":"education","lineage":["https://openalex.org/I99065089"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Shihan Xie","raw_affiliation_strings":["National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China","Tsinghua Institute of Multidisciplinary Biomedical Research","Tsinghua University"],"affiliations":[{"raw_affiliation_string":"National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China","institution_ids":["https://openalex.org/I4210086405"]},{"raw_affiliation_string":"Tsinghua Institute of Multidisciplinary Biomedical Research","institution_ids":[]},{"raw_affiliation_string":"Tsinghua University","institution_ids":["https://openalex.org/I99065089"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040344252","display_name":"Hui Zhu","orcid":"https://orcid.org/0000-0002-4024-374X"},"institutions":[{"id":"https://openalex.org/I4210086405","display_name":"National Institute of Biological Sciences, Beijing","ror":"https://ror.org/00wksha49","country_code":"CN","type":"facility","lineage":["https://openalex.org/I4210086405"]},{"id":"https://openalex.org/I99065089","display_name":"Tsinghua University","ror":"https://ror.org/03cve4549","country_code":"CN","type":"education","lineage":["https://openalex.org/I99065089"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Hui Zhu","raw_affiliation_strings":["National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China","Tsinghua Institute of Multidisciplinary Biomedical Research","Tsinghua University"],"affiliations":[{"raw_affiliation_string":"National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China","institution_ids":["https://openalex.org/I4210086405"]},{"raw_affiliation_string":"Tsinghua Institute of Multidisciplinary Biomedical Research","institution_ids":[]},{"raw_affiliation_string":"Tsinghua University","institution_ids":["https://openalex.org/I99065089"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5074665620","display_name":"Niu Huang","orcid":"https://orcid.org/0000-0002-6912-033X"},"institutions":[{"id":"https://openalex.org/I4210086405","display_name":"National Institute of Biological Sciences, Beijing","ror":"https://ror.org/00wksha49","country_code":"CN","type":"facility","lineage":["https://openalex.org/I4210086405"]},{"id":"https://openalex.org/I99065089","display_name":"Tsinghua University","ror":"https://ror.org/03cve4549","country_code":"CN","type":"education","lineage":["https://openalex.org/I99065089"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Niu Huang","raw_affiliation_strings":["National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China","Tsinghua Institute of Multidisciplinary Biomedical Research","Tsinghua University"],"affiliations":[{"raw_affiliation_string":"National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China","institution_ids":["https://openalex.org/I4210086405"]},{"raw_affiliation_string":"Tsinghua Institute of Multidisciplinary Biomedical Research","institution_ids":[]},{"raw_affiliation_string":"Tsinghua University","institution_ids":["https://openalex.org/I99065089"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5074665620"],"corresponding_institution_ids":["https://openalex.org/I4210086405","https://openalex.org/I99065089"],"apc_list":null,"apc_paid":null,"fwci":12.0667,"has_fulltext":false,"cited_by_count":8,"citation_normalized_percentile":{"value":0.98663458,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":96,"max":100},"biblio":{"volume":"65","issue":"17","first_page":"8924","last_page":"8933"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9998999834060669,"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":0.9998999834060669,"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/T11948","display_name":"Machine Learning in Materials Science","score":0.9976999759674072,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.9139999747276306,"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":0.8002616167068481},{"id":"https://openalex.org/keywords/novelty","display_name":"Novelty","score":0.7963161468505859},{"id":"https://openalex.org/keywords/drug","display_name":"Drug","score":0.45334291458129883},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.3963259756565094},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.3551126718521118},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.3055597245693207},{"id":"https://openalex.org/keywords/medicine","display_name":"Medicine","score":0.23892438411712646},{"id":"https://openalex.org/keywords/pharmacology","display_name":"Pharmacology","score":0.20148834586143494},{"id":"https://openalex.org/keywords/psychology","display_name":"Psychology","score":0.19678309559822083},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.12902522087097168},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.07751509547233582}],"concepts":[{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.8002616167068481},{"id":"https://openalex.org/C2778738651","wikidata":"https://www.wikidata.org/wiki/Q16546687","display_name":"Novelty","level":2,"score":0.7963161468505859},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.45334291458129883},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3963259756565094},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3551126718521118},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3055597245693207},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.23892438411712646},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.20148834586143494},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.19678309559822083},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.12902522087097168},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.07751509547233582},{"id":"https://openalex.org/C77805123","wikidata":"https://www.wikidata.org/wiki/Q161272","display_name":"Social psychology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D001185","descriptor_name":"Artificial Intelligence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D001185","descriptor_name":"Artificial Intelligence","qualifier_ui":null,"qualifier_name":null,"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":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5c00921","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00921","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:40820734","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40820734","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":[{"id":"https://openalex.org/G3487226201","display_name":null,"funder_award_id":"Z211100003321007","funder_id":"https://openalex.org/F4320325902","funder_display_name":"Beijing Municipal Science and Technology Commission"}],"funders":[{"id":"https://openalex.org/F4320322392","display_name":"Tsinghua University","ror":"https://ror.org/03cve4549"},{"id":"https://openalex.org/F4320325902","display_name":"Beijing Municipal Science and Technology Commission","ror":null}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":104,"referenced_works":["https://openalex.org/W1974880836","https://openalex.org/W1975147762","https://openalex.org/W1983478747","https://openalex.org/W1988037271","https://openalex.org/W1993285168","https://openalex.org/W2001580341","https://openalex.org/W2009459159","https://openalex.org/W2016979469","https://openalex.org/W2027173571","https://openalex.org/W2092285329","https://openalex.org/W2096541451","https://openalex.org/W2114162221","https://openalex.org/W2119512897","https://openalex.org/W2121365495","https://openalex.org/W2132629607","https://openalex.org/W2155159115","https://openalex.org/W2166550586","https://openalex.org/W2274656763","https://openalex.org/W2472085920","https://openalex.org/W2587598315","https://openalex.org/W2589798814","https://openalex.org/W2600249486","https://openalex.org/W2784270883","https://openalex.org/W2791355014","https://openalex.org/W2807907860","https://openalex.org/W2897337442","https://openalex.org/W2912171584","https://openalex.org/W2919354330","https://openalex.org/W2923693308","https://openalex.org/W2951737599","https://openalex.org/W2971690404","https://openalex.org/W2974531988","https://openalex.org/W2985233215","https://openalex.org/W3001433048","https://openalex.org/W3005392824","https://openalex.org/W3007309629","https://openalex.org/W3009999522","https://openalex.org/W3043660595","https://openalex.org/W3080588469","https://openalex.org/W3082411326","https://openalex.org/W3094686696","https://openalex.org/W3097677999","https://openalex.org/W3098189759","https://openalex.org/W3147983081","https://openalex.org/W3195018986","https://openalex.org/W4200289210","https://openalex.org/W4210617107","https://openalex.org/W4223439938","https://openalex.org/W4280535976","https://openalex.org/W4283070054","https://openalex.org/W4283782816","https://openalex.org/W4288055522","https://openalex.org/W4296128995","https://openalex.org/W4297995910","https://openalex.org/W4306728530","https://openalex.org/W4306976400","https://openalex.org/W4306986475","https://openalex.org/W4309047034","https://openalex.org/W4311612485","https://openalex.org/W4313551409","https://openalex.org/W4313703391","https://openalex.org/W4313880353","https://openalex.org/W4323650483","https://openalex.org/W4362716857","https://openalex.org/W4366999386","https://openalex.org/W4367672738","https://openalex.org/W4368362970","https://openalex.org/W4372330430","https://openalex.org/W4378072282","https://openalex.org/W4378212018","https://openalex.org/W4378802816","https://openalex.org/W4379016428","https://openalex.org/W4380739447","https://openalex.org/W4381547631","https://openalex.org/W4382813033","https://openalex.org/W4385407581","https://openalex.org/W4385684148","https://openalex.org/W4387561067","https://openalex.org/W4388327645","https://openalex.org/W4388455891","https://openalex.org/W4388760289","https://openalex.org/W4389681077","https://openalex.org/W4390221451","https://openalex.org/W4390232451","https://openalex.org/W4390605827","https://openalex.org/W4390671573","https://openalex.org/W4391133512","https://openalex.org/W4392015344","https://openalex.org/W4392596618","https://openalex.org/W4392653998","https://openalex.org/W4392822048","https://openalex.org/W4393036333","https://openalex.org/W4393222489","https://openalex.org/W4394994059","https://openalex.org/W4396660597","https://openalex.org/W4396768244","https://openalex.org/W4399589608","https://openalex.org/W4400112692","https://openalex.org/W4401051931","https://openalex.org/W4402273478","https://openalex.org/W4403891981","https://openalex.org/W4405841727","https://openalex.org/W4406179976","https://openalex.org/W4406633314"],"related_works":["https://openalex.org/W2948807893","https://openalex.org/W2899084033","https://openalex.org/W2778153218","https://openalex.org/W2748952813","https://openalex.org/W1531601525","https://openalex.org/W2013003323","https://openalex.org/W1981076832","https://openalex.org/W2024773645","https://openalex.org/W2001717001","https://openalex.org/W2043147644"],"abstract_inverted_index":{"Achieving":[0],"structural":[1,49,122],"novelty":[2,50,70,113,142],"in":[3,17,59,74,165],"drug":[4,131,167],"discovery":[5,132,168],"remains":[6],"a":[7],"critical":[8],"challenge.":[9],"Artificial":[10],"intelligence":[11],"(AI)":[12],"has":[13],"demonstrated":[14],"remarkable":[15],"potential":[16],"deciphering":[18],"the":[19,48,93,135,148],"complex":[20],"relationships":[21],"between":[22],"molecular":[23],"structures":[24],"and":[25,32,115,133,143,159],"activities":[26],"from":[27,99],"vast":[28],"amounts":[29],"of":[30,51,76,150,162],"chemical":[31,41],"biological":[33],"information.":[34],"However,":[35,102],"its":[36],"ability":[37],"to":[38,108,120,140],"explore":[39],"novel":[40],"spaces":[42],"is":[43],"underexplored.":[44],"This":[45,124],"study":[46],"evaluates":[47],"AI-designed":[52],"active":[53],"compounds":[54],"across":[55],"71":[56],"cases":[57],"published":[58],"recent":[60],"years.":[61],"Ligand-based":[62],"models":[63],"often":[64],"yield":[65],"molecules":[66],"with":[67,85,95],"relatively":[68],"low":[69],"(Tc<sub>max</sub>":[71],">":[72,87],"0.4":[73],"58.1%":[75],"cases),":[77],"whereas":[78],"structure-based":[79,100],"approaches":[80],"exhibit":[81],"better":[82],"performance":[83],"(17.9%":[84],"Tc<sub>max</sub>":[86],"0.4).":[88],"Screening":[89],"workflows":[90],"significantly":[91],"influence":[92],"novelty,":[94],"underexplored":[96],"targets":[97],"benefiting":[98],"methods.":[101],"fingerprint-based":[103],"similarity":[104,157,163],"metrics":[105],"may":[106],"fail":[107],"detect":[109],"scaffold-level":[110],"similarities.":[111],"Systematic":[112],"assessment":[114],"manual":[116],"verification":[117],"are":[118],"essential":[119],"avoid":[121],"homogenization.":[123],"Review":[125],"provides":[126],"insights":[127],"for":[128,137],"optimizing":[129],"AI-driven":[130,166],"underscores":[134],"need":[136],"interdisciplinary":[138],"collaboration":[139],"balance":[141],"activity.":[144],"Specifically,":[145],"we":[146],"recommend":[147],"use":[149],"diverse":[151],"training":[152],"data":[153],"sets,":[154],"scaffold-hopping":[155],"aware":[156],"metrics,":[158],"careful":[160],"consideration":[161],"filters":[164],"workflows.":[169]},"counts_by_year":[{"year":2026,"cited_by_count":5},{"year":2025,"cited_by_count":3}],"updated_date":"2026-03-27T05:58:40.876381","created_date":"2025-10-10T00:00:00"}