{"id":"https://openalex.org/W4280510131","doi":"https://doi.org/10.1021/acs.jcim.2c00462","title":"An <i>In Silico</i> Explainable Multiparameter Optimization Approach for <i>De Novo</i> Drug Design against Proteins from the Central Nervous System","display_name":"An <i>In Silico</i> Explainable Multiparameter Optimization Approach for <i>De Novo</i> Drug Design against Proteins from the Central Nervous System","publication_year":2022,"publication_date":"2022-05-17","ids":{"openalex":"https://openalex.org/W4280510131","doi":"https://doi.org/10.1021/acs.jcim.2c00462","pmid":"https://pubmed.ncbi.nlm.nih.gov/35581002"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.2c00462","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.2c00462","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/A5027584199","display_name":"Navneet Bung","orcid":"https://orcid.org/0000-0002-6376-277X"},"institutions":[{"id":"https://openalex.org/I55215948","display_name":"Tata Consultancy Services (India)","ror":"https://ror.org/01b9n8m42","country_code":"IN","type":"company","lineage":["https://openalex.org/I4210086519","https://openalex.org/I55215948"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Navneet Bung","raw_affiliation_strings":["TCS Research (Life Sciences Division), Tata Consultancy Services Limited, Hyderabad 500081, India"],"raw_orcid":"https://orcid.org/0000-0002-6376-277X","affiliations":[{"raw_affiliation_string":"TCS Research (Life Sciences Division), Tata Consultancy Services Limited, Hyderabad 500081, India","institution_ids":["https://openalex.org/I55215948"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102810785","display_name":"Sowmya Ramaswamy Krishnan","orcid":"https://orcid.org/0000-0001-5404-3266"},"institutions":[{"id":"https://openalex.org/I55215948","display_name":"Tata Consultancy Services (India)","ror":"https://ror.org/01b9n8m42","country_code":"IN","type":"company","lineage":["https://openalex.org/I4210086519","https://openalex.org/I55215948"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Sowmya Ramaswamy Krishnan","raw_affiliation_strings":["TCS Research (Life Sciences Division), Tata Consultancy Services Limited, Hyderabad 500081, India"],"raw_orcid":"https://orcid.org/0000-0001-5404-3266","affiliations":[{"raw_affiliation_string":"TCS Research (Life Sciences Division), Tata Consultancy Services Limited, Hyderabad 500081, India","institution_ids":["https://openalex.org/I55215948"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5042990614","display_name":"Arijit Roy","orcid":"https://orcid.org/0000-0002-1961-2483"},"institutions":[{"id":"https://openalex.org/I55215948","display_name":"Tata Consultancy Services (India)","ror":"https://ror.org/01b9n8m42","country_code":"IN","type":"company","lineage":["https://openalex.org/I4210086519","https://openalex.org/I55215948"]}],"countries":["IN"],"is_corresponding":true,"raw_author_name":"Arijit Roy","raw_affiliation_strings":["TCS Research (Life Sciences Division), Tata Consultancy Services Limited, Hyderabad 500081, India"],"raw_orcid":"https://orcid.org/0000-0002-1961-2483","affiliations":[{"raw_affiliation_string":"TCS Research (Life Sciences Division), Tata Consultancy Services Limited, Hyderabad 500081, India","institution_ids":["https://openalex.org/I55215948"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5042990614"],"corresponding_institution_ids":["https://openalex.org/I55215948"],"apc_list":null,"apc_paid":null,"fwci":3.0485,"has_fulltext":false,"cited_by_count":25,"citation_normalized_percentile":{"value":0.92456699,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":96,"max":99},"biblio":{"volume":"62","issue":"11","first_page":"2685","last_page":"2695"},"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/T10044","display_name":"Protein Structure and Dynamics","score":0.9758999943733215,"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"}},{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9599000215530396,"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/in-silico","display_name":"In silico","score":0.8890799283981323},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.6411882638931274},{"id":"https://openalex.org/keywords/drug","display_name":"Drug","score":0.5836696624755859},{"id":"https://openalex.org/keywords/central-nervous-system","display_name":"Central nervous system","score":0.49583563208580017},{"id":"https://openalex.org/keywords/drug-discovery","display_name":"Drug discovery","score":0.472780704498291},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.3825986683368683},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.37339797616004944},{"id":"https://openalex.org/keywords/bioinformatics","display_name":"Bioinformatics","score":0.29293927550315857},{"id":"https://openalex.org/keywords/neuroscience","display_name":"Neuroscience","score":0.2774481177330017},{"id":"https://openalex.org/keywords/pharmacology","display_name":"Pharmacology","score":0.2725033760070801},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.16935893893241882}],"concepts":[{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.8890799283981323},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.6411882638931274},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.5836696624755859},{"id":"https://openalex.org/C529278444","wikidata":"https://www.wikidata.org/wiki/Q47273","display_name":"Central nervous system","level":2,"score":0.49583563208580017},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.472780704498291},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3825986683368683},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.37339797616004944},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.29293927550315857},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.2774481177330017},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.2725033760070801},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.16935893893241882},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D001812","descriptor_name":"Blood-Brain Barrier","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001812","descriptor_name":"Blood-Brain Barrier","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001812","descriptor_name":"Blood-Brain Barrier","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002490","descriptor_name":"Central Nervous System","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002490","descriptor_name":"Central Nervous System","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002490","descriptor_name":"Central Nervous System","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002491","descriptor_name":"Central Nervous System Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D002491","descriptor_name":"Central Nervous System Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D002491","descriptor_name":"Central Nervous System Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D002491","descriptor_name":"Central Nervous System Agents","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D002491","descriptor_name":"Central Nervous System Agents","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D002491","descriptor_name":"Central Nervous System Agents","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"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":"D006801","descriptor_name":"Humans","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}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.2c00462","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.2c00462","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:35581002","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/35581002","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":[{"display_name":"Good health and well-being","score":0.7200000286102295,"id":"https://metadata.un.org/sdg/3"}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":48,"referenced_works":["https://openalex.org/W34002366","https://openalex.org/W1500036797","https://openalex.org/W1505823450","https://openalex.org/W1991054810","https://openalex.org/W2009038792","https://openalex.org/W2011188338","https://openalex.org/W2021431618","https://openalex.org/W2030215451","https://openalex.org/W2032065659","https://openalex.org/W2038702914","https://openalex.org/W2043509228","https://openalex.org/W2048277731","https://openalex.org/W2057569612","https://openalex.org/W2113364934","https://openalex.org/W2114650590","https://openalex.org/W2134967712","https://openalex.org/W2165168652","https://openalex.org/W2255345601","https://openalex.org/W2300160852","https://openalex.org/W2319060767","https://openalex.org/W2578240541","https://openalex.org/W2593632281","https://openalex.org/W2594183968","https://openalex.org/W2610148085","https://openalex.org/W2773987374","https://openalex.org/W2786822500","https://openalex.org/W2789328564","https://openalex.org/W2794994220","https://openalex.org/W2887280559","https://openalex.org/W2897337442","https://openalex.org/W2900694120","https://openalex.org/W2949986955","https://openalex.org/W2952524552","https://openalex.org/W2956961449","https://openalex.org/W2971690404","https://openalex.org/W3000348967","https://openalex.org/W3007309629","https://openalex.org/W3008526009","https://openalex.org/W3019676419","https://openalex.org/W3090171308","https://openalex.org/W3100358278","https://openalex.org/W3100751385","https://openalex.org/W3125566655","https://openalex.org/W3174777205","https://openalex.org/W3179318616","https://openalex.org/W4214567217","https://openalex.org/W4249605295","https://openalex.org/W6816747942"],"related_works":["https://openalex.org/W2003194288","https://openalex.org/W2513589746","https://openalex.org/W2153919606","https://openalex.org/W2213189664","https://openalex.org/W2074002899","https://openalex.org/W2062254828","https://openalex.org/W4237480606","https://openalex.org/W2936968863","https://openalex.org/W2941821699","https://openalex.org/W1971792277"],"abstract_inverted_index":{"The":[0,129,179,204],"aim":[1],"of":[2,56,97,105,181,193,199,219,226],"drug":[3,11,57,69,177],"design":[4,58,70,74,186,212],"and":[5,18,23,38,40,59,164],"development":[6],"is":[7,28],"to":[8,49,101,118,154,211,216],"produce":[9],"a":[10,20,29,64,91,142],"that":[12,72,231],"can":[13,73],"inhibit":[14],"the":[15,103,109,120,125,135,145,161,191,223,227,233],"target":[16,80,162],"protein":[17,143],"possess":[19],"balanced":[21],"physicochemical":[22,39,151],"toxicity":[24],"profile.":[25],"Traditionally,":[26],"this":[27],"multistep":[30],"process":[31],"where":[32],"different":[33],"parameters":[34,86,98],"such":[35],"as":[36,82,84,171],"activity":[37],"pharmacokinetic":[41],"properties":[42,152,192],"are":[43],"optimized":[44,100,206],"sequentially,":[45],"which":[46,169],"often":[47],"leads":[48],"high":[50],"attrition":[51],"rate":[52],"during":[53],"later":[54],"stages":[55],"development.":[60],"We":[61],"have":[62],"developed":[63],"deep":[65],"learning-based":[66],"de":[67],"novo":[68],"method":[71,131],"novel":[75],"small":[76,195,229],"molecules":[77,196,230],"by":[78,189],"optimizing":[79],"specificity":[81,163],"well":[83],"multiple":[85],"(including":[87],"late-stage":[88],"parameters)":[89],"in":[90],"single":[92],"step.":[93],"All":[94],"possible":[95,201],"combinations":[96],"were":[99,157,237],"understand":[102],"effect":[104],"each":[106,182],"parameter":[107,183,202],"over":[108],"other":[110],"parameters.":[111],"An":[112],"explainable":[113],"predictive":[114,235],"model":[115,208,236],"was":[116,132,187,209],"used":[117],"identify":[119],"molecular":[121],"fragments":[122],"responsible":[123],"for":[124,175],"property":[126],"being":[127],"optimized.":[128],"proposed":[130],"applied":[133],"against":[134],"human":[136],"5-hydroxy":[137],"tryptamine":[138],"receptor":[139],"1B":[140],"(5-HT1B),":[141],"from":[144,197],"central":[146],"nervous":[147],"system":[148],"(CNS).":[149],"Various":[150],"specific":[153],"CNS":[155,176],"drugs":[156],"considered":[158],"along":[159],"with":[160],"blood\u2013brain":[165],"barrier":[166],"permeability":[167],"(BBBP),":[168],"act":[170],"an":[172],"additional":[173],"challenge":[174],"delivery.":[178],"contribution":[180],"toward":[184],"molecule":[185],"identified":[188,238],"analyzing":[190],"generated":[194,228],"optimization":[198],"all":[200],"combinations.":[203],"final":[205],"generative":[207],"able":[210],"similar":[213],"inhibitors":[214,218],"compared":[215],"known":[217],"5-HT1B.":[220],"In":[221],"addition,":[222],"functional":[224],"groups":[225],"guide":[232],"BBBP":[234],"through":[239],"feature":[240],"attribution":[241],"techniques.":[242]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":11},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":6},{"year":2022,"cited_by_count":3}],"updated_date":"2026-07-15T18:14:33.161393","created_date":"2025-10-10T00:00:00"}