{"id":"https://openalex.org/W4417151640","doi":"https://doi.org/10.1021/acs.jcim.5c02316","title":"Test-Time Training Scaling Laws for Chemical Exploration in Drug Design","display_name":"Test-Time Training Scaling Laws for Chemical Exploration in Drug Design","publication_year":2025,"publication_date":"2025-12-09","ids":{"openalex":"https://openalex.org/W4417151640","doi":"https://doi.org/10.1021/acs.jcim.5c02316","pmid":"https://pubmed.ncbi.nlm.nih.gov/41363014"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c02316","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c02316","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","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":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1021/acs.jcim.5c02316","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5064256420","display_name":"Morgan Thomas","orcid":"https://orcid.org/0000-0002-1610-3499"},"institutions":[{"id":"https://openalex.org/I170486558","display_name":"Universitat Pompeu Fabra","ror":"https://ror.org/04n0g0b29","country_code":"ES","type":"education","lineage":["https://openalex.org/I170486558"]},{"id":"https://openalex.org/I176601375","display_name":"Khalifa University of Science and Technology","ror":"https://ror.org/05hffr360","country_code":"AE","type":"education","lineage":["https://openalex.org/I176601375"]},{"id":"https://openalex.org/I2801864671","display_name":"Barcelona Biomedical Research Park","ror":"https://ror.org/05sajct49","country_code":"ES","type":"facility","lineage":["https://openalex.org/I2801864671"]}],"countries":["AE","ES"],"is_corresponding":true,"raw_author_name":"Morgan Thomas","raw_affiliation_strings":["Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), C Dr. Aiguader 88, 08003 Barcelona, Spain","Department of Medical Sciences","Khalifa University of Science and Technology","Department of Medical Sciences, Khalifa University of Science and Technology, 127788 Abu Dhabi, UAE"],"raw_orcid":"https://orcid.org/0000-0002-1610-3499","affiliations":[{"raw_affiliation_string":"Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), C Dr. Aiguader 88, 08003 Barcelona, Spain","institution_ids":["https://openalex.org/I2801864671","https://openalex.org/I170486558"]},{"raw_affiliation_string":"Department of Medical Sciences","institution_ids":[]},{"raw_affiliation_string":"Khalifa University of Science and Technology","institution_ids":["https://openalex.org/I176601375"]},{"raw_affiliation_string":"Department of Medical Sciences, Khalifa University of Science and Technology, 127788 Abu Dhabi, UAE","institution_ids":["https://openalex.org/I176601375"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020298420","display_name":"Albert Bou","orcid":"https://orcid.org/0000-0001-6027-4538"},"institutions":[{"id":"https://openalex.org/I170486558","display_name":"Universitat Pompeu Fabra","ror":"https://ror.org/04n0g0b29","country_code":"ES","type":"education","lineage":["https://openalex.org/I170486558"]},{"id":"https://openalex.org/I2801864671","display_name":"Barcelona Biomedical Research Park","ror":"https://ror.org/05sajct49","country_code":"ES","type":"facility","lineage":["https://openalex.org/I2801864671"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Albert Bou","raw_affiliation_strings":["Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), C Dr. Aiguader 88, 08003 Barcelona, Spain"],"raw_orcid":"https://orcid.org/0000-0001-6027-4538","affiliations":[{"raw_affiliation_string":"Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), C Dr. Aiguader 88, 08003 Barcelona, Spain","institution_ids":["https://openalex.org/I2801864671","https://openalex.org/I170486558"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5027026045","display_name":"Gianni De Fabritiis","orcid":"https://orcid.org/0000-0003-3913-4877"},"institutions":[{"id":"https://openalex.org/I11932220","display_name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats","ror":"https://ror.org/0371hy230","country_code":"ES","type":"nonprofit","lineage":["https://openalex.org/I11932220"]},{"id":"https://openalex.org/I170486558","display_name":"Universitat Pompeu Fabra","ror":"https://ror.org/04n0g0b29","country_code":"ES","type":"education","lineage":["https://openalex.org/I170486558"]},{"id":"https://openalex.org/I2801864671","display_name":"Barcelona Biomedical Research Park","ror":"https://ror.org/05sajct49","country_code":"ES","type":"facility","lineage":["https://openalex.org/I2801864671"]},{"id":"https://openalex.org/I4210153560","display_name":"Acellera (Spain)","ror":"https://ror.org/051pfzb30","country_code":"ES","type":"company","lineage":["https://openalex.org/I4210153560"]}],"countries":["ES"],"is_corresponding":true,"raw_author_name":"Gianni De Fabritiis","raw_affiliation_strings":["Acellera Labs, C Dr Trueta 183, 08005 Barcelona, Spain","Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), C Dr. Aiguader 88, 08003 Barcelona, Spain","Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain"],"raw_orcid":"https://orcid.org/0000-0003-3913-4877","affiliations":[{"raw_affiliation_string":"Acellera Labs, C Dr Trueta 183, 08005 Barcelona, Spain","institution_ids":["https://openalex.org/I4210153560"]},{"raw_affiliation_string":"Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), C Dr. Aiguader 88, 08003 Barcelona, Spain","institution_ids":["https://openalex.org/I2801864671","https://openalex.org/I170486558"]},{"raw_affiliation_string":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain","institution_ids":["https://openalex.org/I11932220"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5027026045","https://openalex.org/A5064256420"],"corresponding_institution_ids":["https://openalex.org/I11932220","https://openalex.org/I170486558","https://openalex.org/I176601375","https://openalex.org/I2801864671","https://openalex.org/I4210153560"],"apc_list":null,"apc_paid":null,"fwci":0.9179,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.76839959,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":91,"max":98},"biblio":{"volume":"65","issue":"24","first_page":"13178","last_page":"13186"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11948","display_name":"Machine Learning in Materials Science","score":0.8859000205993652,"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"}},"topics":[{"id":"https://openalex.org/T11948","display_name":"Machine Learning in Materials Science","score":0.8859000205993652,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.0681999996304512,"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/T11273","display_name":"Advanced Graph Neural Networks","score":0.0034000000450760126,"subfield":{"id":"https://openalex.org/subfields/1702","display_name":"Artificial Intelligence"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/scalability","display_name":"Scalability","score":0.8004000186920166},{"id":"https://openalex.org/keywords/chemical-space","display_name":"Chemical space","score":0.7508999705314636},{"id":"https://openalex.org/keywords/benchmark","display_name":"Benchmark (surveying)","score":0.6880000233650208},{"id":"https://openalex.org/keywords/limiting","display_name":"Limiting","score":0.684499979019165},{"id":"https://openalex.org/keywords/scaling","display_name":"Scaling","score":0.6614000201225281},{"id":"https://openalex.org/keywords/reinforcement-learning","display_name":"Reinforcement learning","score":0.6407999992370605},{"id":"https://openalex.org/keywords/generative-grammar","display_name":"Generative grammar","score":0.489300012588501},{"id":"https://openalex.org/keywords/training","display_name":"Training (meteorology)","score":0.43799999356269836}],"concepts":[{"id":"https://openalex.org/C48044578","wikidata":"https://www.wikidata.org/wiki/Q727490","display_name":"Scalability","level":2,"score":0.8004000186920166},{"id":"https://openalex.org/C99726746","wikidata":"https://www.wikidata.org/wiki/Q906396","display_name":"Chemical space","level":3,"score":0.7508999705314636},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.7366999983787537},{"id":"https://openalex.org/C185798385","wikidata":"https://www.wikidata.org/wiki/Q1161707","display_name":"Benchmark (surveying)","level":2,"score":0.6880000233650208},{"id":"https://openalex.org/C188198153","wikidata":"https://www.wikidata.org/wiki/Q1613840","display_name":"Limiting","level":2,"score":0.684499979019165},{"id":"https://openalex.org/C99844830","wikidata":"https://www.wikidata.org/wiki/Q102441924","display_name":"Scaling","level":2,"score":0.6614000201225281},{"id":"https://openalex.org/C97541855","wikidata":"https://www.wikidata.org/wiki/Q830687","display_name":"Reinforcement learning","level":2,"score":0.6407999992370605},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.5184000134468079},{"id":"https://openalex.org/C39890363","wikidata":"https://www.wikidata.org/wiki/Q36108","display_name":"Generative grammar","level":2,"score":0.489300012588501},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.4494999945163727},{"id":"https://openalex.org/C2777211547","wikidata":"https://www.wikidata.org/wiki/Q17141490","display_name":"Training (meteorology)","level":2,"score":0.43799999356269836},{"id":"https://openalex.org/C2778572836","wikidata":"https://www.wikidata.org/wiki/Q380933","display_name":"Space (punctuation)","level":2,"score":0.39890000224113464},{"id":"https://openalex.org/C2988430800","wikidata":"https://www.wikidata.org/wiki/Q428971","display_name":"Scaling law","level":3,"score":0.35249999165534973},{"id":"https://openalex.org/C51632099","wikidata":"https://www.wikidata.org/wiki/Q3985153","display_name":"Training set","level":2,"score":0.3472999930381775},{"id":"https://openalex.org/C48677424","wikidata":"https://www.wikidata.org/wiki/Q6888088","display_name":"Mode (computer interface)","level":2,"score":0.30809998512268066},{"id":"https://openalex.org/C183696295","wikidata":"https://www.wikidata.org/wiki/Q2487696","display_name":"Biochemical engineering","level":1,"score":0.2879999876022339},{"id":"https://openalex.org/C167966045","wikidata":"https://www.wikidata.org/wiki/Q5532625","display_name":"Generative model","level":3,"score":0.28630000352859497},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.2745000123977661},{"id":"https://openalex.org/C2522767166","wikidata":"https://www.wikidata.org/wiki/Q2374463","display_name":"Data science","level":1,"score":0.26330000162124634},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.25609999895095825},{"id":"https://openalex.org/C80444323","wikidata":"https://www.wikidata.org/wiki/Q2878974","display_name":"Theoretical computer science","level":1,"score":0.25220000743865967},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.25189998745918274}],"mesh":[{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","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":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"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":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.5c02316","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c02316","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:41363014","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41363014","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},{"id":"pmh:oai:pubmedcentral.nih.gov:12728925","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12728925/","pdf_url":null,"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,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1021/acs.jcim.5c02316","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c02316","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G8530933779","display_name":null,"funder_award_id":"HBC.2021.1123","funder_id":"https://openalex.org/F4320313460","funder_display_name":"Agentschap Innoveren en Ondernemen"}],"funders":[{"id":"https://openalex.org/F4320313460","display_name":"Agentschap Innoveren en Ondernemen","ror":"https://ror.org/032xdry56"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":36,"referenced_works":["https://openalex.org/W1975147762","https://openalex.org/W2023818227","https://openalex.org/W2578240541","https://openalex.org/W2610148085","https://openalex.org/W2773987374","https://openalex.org/W2809247499","https://openalex.org/W2887447356","https://openalex.org/W2900694120","https://openalex.org/W2925830236","https://openalex.org/W2947161483","https://openalex.org/W2968526727","https://openalex.org/W3043096321","https://openalex.org/W3094553402","https://openalex.org/W3103098434","https://openalex.org/W3113150977","https://openalex.org/W3116865743","https://openalex.org/W3133989558","https://openalex.org/W3185391990","https://openalex.org/W3198869316","https://openalex.org/W4283787033","https://openalex.org/W4285797776","https://openalex.org/W4300861533","https://openalex.org/W4310603653","https://openalex.org/W4318952054","https://openalex.org/W4381053688","https://openalex.org/W4389681077","https://openalex.org/W4394023619","https://openalex.org/W4394683604","https://openalex.org/W4399175418","https://openalex.org/W4400320632","https://openalex.org/W4400860798","https://openalex.org/W4400876473","https://openalex.org/W4401255931","https://openalex.org/W4402672014","https://openalex.org/W4403302853","https://openalex.org/W4416263560"],"related_works":[],"abstract_inverted_index":{"Chemical":[0],"language":[1,33],"models":[2],"(CLMs)":[3],"leveraging":[4],"reinforcement":[5],"learning":[6],"(RL)":[7],"have":[8],"shown":[9],"promise":[10],"in":[11,31],"de":[12],"novo":[13],"molecular":[14,125],"design,":[15,126],"yet":[16],"often":[17],"suffer":[18],"from":[19],"mode":[20],"collapse,":[21],"limiting":[22],"their":[23],"exploration":[24,88,105,115],"capabilities.":[25],"Inspired":[26],"by":[27,73,92],"test-time":[28],"training":[29,98],"(TTT)":[30],"large":[32],"models,":[34],"we":[35],"propose":[36],"scaling":[37,71,84],"TTT":[38,72,97],"for":[39,123],"CLMs":[40],"to":[41,113],"enhance":[42,114],"chemical":[43],"space":[44],"exploration.":[45],"We":[46,107],"introduce":[47],"MolExp,":[48],"a":[49,82,120],"novel":[50],"benchmark":[51],"emphasizing":[52],"the":[53,75],"discovery":[54],"of":[55,77],"structurally":[56],"diverse":[57],"molecules":[58],"with":[59,104],"similar":[60],"bioactivity,":[61],"simulating":[62],"real-world":[63],"drug":[64,132],"design":[65],"challenges.":[66],"Our":[67],"results":[68],"demonstrate":[69],"that":[70],"increasing":[74,96],"number":[76],"independent":[78],"RL":[79,111],"agents":[80],"follows":[81],"log-linear":[83],"law,":[85],"significantly":[86],"improving":[87],"efficiency":[89],"as":[90],"measured":[91],"MolExp.":[93],"In":[94],"contrast,":[95],"time":[99],"yields":[100],"diminishing":[101],"returns,":[102],"even":[103],"bonuses.":[106],"further":[108],"evaluate":[109],"cooperative":[110],"strategies":[112],"efficiency.":[116],"These":[117],"findings":[118],"provide":[119],"scalable":[121],"framework":[122],"generative":[124],"offering":[127],"insights":[128],"into":[129],"optimizing":[130],"AI-driven":[131],"discovery.":[133]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1}],"updated_date":"2025-12-23T23:11:35.936235","created_date":"2025-12-09T00:00:00"}
