{"id":"https://openalex.org/W4300861533","doi":"https://doi.org/10.1186/s13321-022-00646-z","title":"Augmented Hill-Climb increases reinforcement learning efficiency for language-based de novo molecule generation","display_name":"Augmented Hill-Climb increases reinforcement learning efficiency for language-based de novo molecule generation","publication_year":2022,"publication_date":"2022-10-03","ids":{"openalex":"https://openalex.org/W4300861533","doi":"https://doi.org/10.1186/s13321-022-00646-z","pmid":"https://pubmed.ncbi.nlm.nih.gov/36192789"},"language":"en","primary_location":{"id":"doi:10.1186/s13321-022-00646-z","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s13321-022-00646-z","pdf_url":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-022-00646-z","source":{"id":"https://openalex.org/S180838163","display_name":"Journal of Cheminformatics","issn_l":"1758-2946","issn":["1758-2946"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"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 Cheminformatics","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-022-00646-z","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/I241749","display_name":"University of Cambridge","ror":"https://ror.org/013meh722","country_code":"GB","type":"education","lineage":["https://openalex.org/I241749"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Morgan Thomas","raw_affiliation_strings":["Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. mct50@cam.ac.uk","Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. mct50@cam.ac.uk","institution_ids":["https://openalex.org/I241749"]},{"raw_affiliation_string":"Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK","institution_ids":["https://openalex.org/I241749"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036721569","display_name":"Noel M. O\u2019Boyle","orcid":"https://orcid.org/0000-0003-4879-2003"},"institutions":[{"id":"https://openalex.org/I4210147697","display_name":"Heptares Therapeutics (United Kingdom)","ror":"https://ror.org/051fk5x88","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210147697"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Noel M. O\u2019Boyle","raw_affiliation_strings":["Computational Chemistry, Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge, CB21 6DG, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Computational Chemistry, Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge, CB21 6DG, UK","institution_ids":["https://openalex.org/I4210147697"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026643759","display_name":"Andreas Bender","orcid":"https://orcid.org/0000-0002-6683-7546"},"institutions":[{"id":"https://openalex.org/I241749","display_name":"University of Cambridge","ror":"https://ror.org/013meh722","country_code":"GB","type":"education","lineage":["https://openalex.org/I241749"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Andreas Bender","raw_affiliation_strings":["Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK","institution_ids":["https://openalex.org/I241749"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5020226245","display_name":"Chris de Graaf","orcid":"https://orcid.org/0000-0002-1226-2150"},"institutions":[{"id":"https://openalex.org/I4210147697","display_name":"Heptares Therapeutics (United Kingdom)","ror":"https://ror.org/051fk5x88","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210147697"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Chris de Graaf","raw_affiliation_strings":["Computational Chemistry, Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge, CB21 6DG, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Computational Chemistry, Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge, CB21 6DG, UK","institution_ids":["https://openalex.org/I4210147697"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5064256420"],"corresponding_institution_ids":["https://openalex.org/I241749"],"apc_list":{"value":1290,"currency":"GBP","value_usd":1582},"apc_paid":{"value":1290,"currency":"GBP","value_usd":1582},"fwci":7.7623,"has_fulltext":true,"cited_by_count":49,"citation_normalized_percentile":{"value":0.97972135,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":99,"max":100},"biblio":{"volume":"14","issue":"1","first_page":"68","last_page":"68"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9991000294685364,"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":0.9991000294685364,"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":0.998199999332428,"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/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9865000247955322,"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/reinforcement-learning","display_name":"Reinforcement learning","score":0.8672288060188293},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.7291725873947144},{"id":"https://openalex.org/keywords/climb","display_name":"Climb","score":0.5992178916931152},{"id":"https://openalex.org/keywords/artificial-intelligence","display_name":"Artificial intelligence","score":0.571979284286499},{"id":"https://openalex.org/keywords/artificial-neural-network","display_name":"Artificial neural network","score":0.4445054233074188},{"id":"https://openalex.org/keywords/machine-learning","display_name":"Machine learning","score":0.4423283040523529},{"id":"https://openalex.org/keywords/reinforcement","display_name":"Reinforcement","score":0.4421887993812561},{"id":"https://openalex.org/keywords/benchmark","display_name":"Benchmark (surveying)","score":0.4413047730922699},{"id":"https://openalex.org/keywords/context","display_name":"Context (archaeology)","score":0.4209796190261841},{"id":"https://openalex.org/keywords/engineering","display_name":"Engineering","score":0.11077728867530823}],"concepts":[{"id":"https://openalex.org/C97541855","wikidata":"https://www.wikidata.org/wiki/Q830687","display_name":"Reinforcement learning","level":2,"score":0.8672288060188293},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.7291725873947144},{"id":"https://openalex.org/C2778168010","wikidata":"https://www.wikidata.org/wiki/Q1499786","display_name":"Climb","level":2,"score":0.5992178916931152},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.571979284286499},{"id":"https://openalex.org/C50644808","wikidata":"https://www.wikidata.org/wiki/Q192776","display_name":"Artificial neural network","level":2,"score":0.4445054233074188},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.4423283040523529},{"id":"https://openalex.org/C67203356","wikidata":"https://www.wikidata.org/wiki/Q1321905","display_name":"Reinforcement","level":2,"score":0.4421887993812561},{"id":"https://openalex.org/C185798385","wikidata":"https://www.wikidata.org/wiki/Q1161707","display_name":"Benchmark (surveying)","level":2,"score":0.4413047730922699},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.4209796190261841},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.11077728867530823},{"id":"https://openalex.org/C13280743","wikidata":"https://www.wikidata.org/wiki/Q131089","display_name":"Geodesy","level":1,"score":0.0},{"id":"https://openalex.org/C205649164","wikidata":"https://www.wikidata.org/wiki/Q1071","display_name":"Geography","level":0,"score":0.0},{"id":"https://openalex.org/C151730666","wikidata":"https://www.wikidata.org/wiki/Q7205","display_name":"Paleontology","level":1,"score":0.0},{"id":"https://openalex.org/C66938386","wikidata":"https://www.wikidata.org/wiki/Q633538","display_name":"Structural engineering","level":1,"score":0.0},{"id":"https://openalex.org/C146978453","wikidata":"https://www.wikidata.org/wiki/Q3798668","display_name":"Aerospace engineering","level":1,"score":0.0},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.1186/s13321-022-00646-z","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s13321-022-00646-z","pdf_url":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-022-00646-z","source":{"id":"https://openalex.org/S180838163","display_name":"Journal of Cheminformatics","issn_l":"1758-2946","issn":["1758-2946"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"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 Cheminformatics","raw_type":"journal-article"},{"id":"pmid:36192789","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/36192789","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 cheminformatics","raw_type":null},{"id":"pmh:oai:doaj.org/article:ef8c92045daf4e0c9567902dbfce2cbf","is_oa":true,"landing_page_url":"https://doaj.org/article/ef8c92045daf4e0c9567902dbfce2cbf","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Journal of Cheminformatics, Vol 14, Iss 1, Pp 1-22 (2022)","raw_type":"article"},{"id":"pmh:oai:pubmedcentral.nih.gov:9531503","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9531503","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 Cheminform","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1186/s13321-022-00646-z","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s13321-022-00646-z","pdf_url":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-022-00646-z","source":{"id":"https://openalex.org/S180838163","display_name":"Journal of Cheminformatics","issn_l":"1758-2946","issn":["1758-2946"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"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 Cheminformatics","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4300861533.pdf","grobid_xml":"https://content.openalex.org/works/W4300861533.grobid-xml"},"referenced_works_count":97,"referenced_works":["https://openalex.org/W61757119","https://openalex.org/W1757990252","https://openalex.org/W1968319881","https://openalex.org/W1973428197","https://openalex.org/W1975147762","https://openalex.org/W1981276685","https://openalex.org/W1985588649","https://openalex.org/W1988037271","https://openalex.org/W2021748110","https://openalex.org/W2027423337","https://openalex.org/W2034549041","https://openalex.org/W2043509228","https://openalex.org/W2055888446","https://openalex.org/W2060531713","https://openalex.org/W2083725367","https://openalex.org/W2097420030","https://openalex.org/W2107160601","https://openalex.org/W2110177837","https://openalex.org/W2117819606","https://openalex.org/W2119717200","https://openalex.org/W2159301944","https://openalex.org/W2302181705","https://openalex.org/W2327581403","https://openalex.org/W2485408402","https://openalex.org/W2529996553","https://openalex.org/W2578240541","https://openalex.org/W2593632281","https://openalex.org/W2594328795","https://openalex.org/W2610148085","https://openalex.org/W2763220183","https://openalex.org/W2773987374","https://openalex.org/W2785023044","https://openalex.org/W2887447356","https://openalex.org/W2896439054","https://openalex.org/W2900694120","https://openalex.org/W2902812092","https://openalex.org/W2912818999","https://openalex.org/W2914542247","https://openalex.org/W2953128081","https://openalex.org/W2956961449","https://openalex.org/W2962764565","https://openalex.org/W2964110616","https://openalex.org/W2971690404","https://openalex.org/W2989615256","https://openalex.org/W2995230747","https://openalex.org/W2997784419","https://openalex.org/W3011286504","https://openalex.org/W3029978182","https://openalex.org/W3043096321","https://openalex.org/W3083024963","https://openalex.org/W3090915092","https://openalex.org/W3094193428","https://openalex.org/W3094553402","https://openalex.org/W3094686696","https://openalex.org/W3098269892","https://openalex.org/W3100358278","https://openalex.org/W3100751385","https://openalex.org/W3103098434","https://openalex.org/W3104956673","https://openalex.org/W3107551345","https://openalex.org/W3108004614","https://openalex.org/W3111168552","https://openalex.org/W3116865743","https://openalex.org/W3125566655","https://openalex.org/W3127493072","https://openalex.org/W3133325765","https://openalex.org/W3133989558","https://openalex.org/W3158331815","https://openalex.org/W3158535672","https://openalex.org/W3162583919","https://openalex.org/W3170120958","https://openalex.org/W3174777205","https://openalex.org/W3198869316","https://openalex.org/W3207373390","https://openalex.org/W3207446095","https://openalex.org/W3209056694","https://openalex.org/W3210833421","https://openalex.org/W3212543990","https://openalex.org/W3213135344","https://openalex.org/W3215957353","https://openalex.org/W4200200013","https://openalex.org/W4200404849","https://openalex.org/W4220887735","https://openalex.org/W4233983546","https://openalex.org/W4235362006","https://openalex.org/W4245443308","https://openalex.org/W4252536872","https://openalex.org/W4281619372","https://openalex.org/W4283270512","https://openalex.org/W4285179478","https://openalex.org/W4304203195","https://openalex.org/W4321377212","https://openalex.org/W4378071155","https://openalex.org/W6605114868","https://openalex.org/W6610423178","https://openalex.org/W6636364444","https://openalex.org/W6835824689"],"related_works":["https://openalex.org/W4296474751","https://openalex.org/W3074294383","https://openalex.org/W1485630101","https://openalex.org/W3153007185","https://openalex.org/W2498017833","https://openalex.org/W4206669594","https://openalex.org/W2961085424","https://openalex.org/W2959276766","https://openalex.org/W4295941380","https://openalex.org/W4319083788"],"abstract_inverted_index":{"Abstract":[0],"A":[1],"plethora":[2],"of":[3,26,115,196,221],"AI-based":[4],"techniques":[5],"now":[6],"exists":[7],"to":[8,36,57,61,64,124,170,188,267],"conduct":[9],"de":[10,44,258],"novo":[11,45,259],"molecule":[12,46,260],"generation":[13,261],"that":[14,108,156,193,203,251],"can":[15,51],"devise":[16],"molecules":[17,60],"conditioned":[18],"towards":[19],"a":[20,38,71,91,100,242,284],"particular":[21],"endpoint":[22],"in":[23,217],"the":[24,113,207,218,268],"context":[25],"drug":[27],"design.":[28],"One":[29],"popular":[30],"approach":[31],"is":[32,159,165],"using":[33,74],"reinforcement":[34,49,92,139,209,243,264],"learning":[35,50,93,140,210,244],"update":[37],"recurrent":[39,236],"neural":[40,237],"network":[41],"or":[42,81,223],"language-based":[43,257],"generator.":[47],"However,":[48],"be":[52,62],"inefficient,":[53],"sometimes":[54],"requiring":[55],"up":[56],"10":[58],"5":[59],"sampled":[63],"optimize":[65,125],"more":[66,225,273,281],"complex":[67],"objectives,":[68],"which":[69],"poses":[70],"limitation":[72],"when":[73],"computationally":[75,274],"expensive":[76,275],"scoring":[77,276],"functions":[78],"like":[79],"docking":[80,127],"computer-aided":[82],"synthesis":[83],"planning":[84],"models.":[85],"In":[86],"this":[87,133],"work,":[88],"we":[89,229,249],"propose":[90],"strategy":[94,134],"called":[95],"Augmented":[96,204,252],"Hill-Climb":[97,107,149,205,253],"based":[98],"on":[99,213,235,241,283],"simple,":[101],"hypothesis-driven":[102],"hybrid":[103],"between":[104],"REINVENT":[105,130,144,171],"and":[106,131,147,150,163,183],"improves":[109,254],"sample-efficiency":[110,164,255],"by":[111],"addressing":[112],"limitations":[114],"both":[116],"currently":[117],"used":[118,138,212],"strategies.":[119],"We":[120,154,201],"compare":[121],"its":[122],"ability":[123,158],"several":[126],"tasks":[128],"with":[129],"benchmark":[132],"against":[135],"other":[136,208],"commonly":[137],"strategies":[141,211],"including":[142],"REINFORCE,":[143],"(version":[145],"1":[146],"2),":[148],"best":[151],"agent":[152],"reminder.":[153],"find":[155,202],"optimization":[157],"improved":[160,166,231],"~":[161,167],"1.5-fold":[162],"45-fold":[168],"compared":[169,266],"while":[172],"still":[173],"delivering":[174],"appealing":[175],"chemistry":[176],"as":[177,279],"output.":[178],"Diversity":[179],"filters":[180],"were":[181,186],"used,":[182],"their":[184],"parameters":[185],"tuned":[187],"overcome":[189],"observed":[190],"failure":[191],"modes":[192],"take":[194],"advantage":[195],"certain":[197],"diversity":[198],"filter":[199],"configurations.":[200],"outperforms":[206],"six":[214],"tasks,":[215],"especially":[216],"early":[219],"stages":[220],"training":[222],"for":[224,256],"difficult":[226],"objectives.":[227],"Lastly,":[228],"show":[230,250],"performance":[232],"not":[233],"only":[234],"networks":[238],"but":[239],"also":[240],"stabilized":[245],"transformer":[246],"architecture.":[247],"Overall,":[248],"conditioning":[262],"via":[263],"learning,":[265],"current":[269],"state-of-the-art.":[270],"This":[271],"makes":[272],"functions,":[277],"such":[278],"docking,":[280],"accessible":[282],"relevant":[285],"timescale.":[286]},"counts_by_year":[{"year":2026,"cited_by_count":8},{"year":2025,"cited_by_count":13},{"year":2024,"cited_by_count":18},{"year":2023,"cited_by_count":10}],"updated_date":"2026-06-19T15:47:20.252518","created_date":"2025-10-10T00:00:00"}
