{"id":"https://openalex.org/W4405912590","doi":"https://doi.org/10.1021/acs.jcim.4c01472","title":"Interpretable Deep-Learning p <i>K</i> <sub>a</sub> Prediction for Small Molecule Drugs via Atomic Sensitivity Analysis","display_name":"Interpretable Deep-Learning p <i>K</i> <sub>a</sub> Prediction for Small Molecule Drugs via Atomic Sensitivity Analysis","publication_year":2024,"publication_date":"2024-12-30","ids":{"openalex":"https://openalex.org/W4405912590","doi":"https://doi.org/10.1021/acs.jcim.4c01472","pmid":"https://pubmed.ncbi.nlm.nih.gov/39801290"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.4c01472","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c01472","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.4c01472","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5012901750","display_name":"Joseph A. DeCorte","orcid":"https://orcid.org/0000-0002-0131-6176"},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]},{"id":"https://openalex.org/I901861585","display_name":"Vanderbilt University Medical Center","ror":"https://ror.org/05dq2gs74","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210162197","https://openalex.org/I901861585"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Joseph DeCorte","raw_affiliation_strings":["Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","Department of Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","Vanderbilt Medical Scientist Training Program, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8725, United States"],"affiliations":[{"raw_affiliation_string":"Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Department of Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Vanderbilt Medical Scientist Training Program, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8725, United States","institution_ids":["https://openalex.org/I901861585"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002038417","display_name":"Benjamin P. Brown","orcid":"https://orcid.org/0000-0001-5296-087X"},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Benjamin Brown","raw_affiliation_strings":["Center for Applied AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232-8725, United States","Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232-8275, United States"],"affiliations":[{"raw_affiliation_string":"Center for Applied AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232-8725, United States","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232-8275, United States","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082620094","display_name":"R. Brooke Jeffrey","orcid":"https://orcid.org/0000-0002-5678-8103"},"institutions":[{"id":"https://openalex.org/I901861585","display_name":"Vanderbilt University Medical Center","ror":"https://ror.org/05dq2gs74","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210162197","https://openalex.org/I901861585"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rathmell Jeffrey","raw_affiliation_strings":["Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States"],"affiliations":[{"raw_affiliation_string":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States","institution_ids":["https://openalex.org/I901861585"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5025842562","display_name":"Jens Meiler","orcid":"https://orcid.org/0000-0001-8945-193X"},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]},{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE","US"],"is_corresponding":false,"raw_author_name":"Jens Meiler","raw_affiliation_strings":["Center for Applied AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232-8725, United States","Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","Department of Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232-8275, United States","Institute for Drug Discovery, Leipzig University Medical School, Leipzig, SAC 04103, Germany"],"affiliations":[{"raw_affiliation_string":"Center for Applied AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232-8725, United States","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Department of Chemical and Physical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232-8275, United States","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"Institute for Drug Discovery, Leipzig University Medical School, Leipzig, SAC 04103, Germany","institution_ids":["https://openalex.org/I926574661"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5012901750"],"corresponding_institution_ids":["https://openalex.org/I200719446","https://openalex.org/I901861585"],"apc_list":null,"apc_paid":null,"fwci":0.7049,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.75828751,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":98,"max":99},"biblio":{"volume":"65","issue":"1","first_page":"101","last_page":"113"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9993000030517578,"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":0.9993000030517578,"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":0.9987000226974487,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.9556999802589417,"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/interpretability","display_name":"Interpretability","score":0.7096450328826904},{"id":"https://openalex.org/keywords/virtual-screening","display_name":"Virtual screening","score":0.5500234961509705},{"id":"https://openalex.org/keywords/leverage","display_name":"Leverage (statistics)","score":0.5331128835678101},{"id":"https://openalex.org/keywords/test-set","display_name":"Test set","score":0.5284654498100281},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.5232716798782349},{"id":"https://openalex.org/keywords/quantitative-structure\u2013activity-relationship","display_name":"Quantitative structure\u2013activity relationship","score":0.5084306597709656},{"id":"https://openalex.org/keywords/molecular-descriptor","display_name":"Molecular descriptor","score":0.499661922454834},{"id":"https://openalex.org/keywords/artificial-intelligence","display_name":"Artificial intelligence","score":0.48818618059158325},{"id":"https://openalex.org/keywords/molecule","display_name":"Molecule","score":0.45779046416282654},{"id":"https://openalex.org/keywords/artificial-neural-network","display_name":"Artificial neural network","score":0.4560326635837555},{"id":"https://openalex.org/keywords/machine-learning","display_name":"Machine learning","score":0.45543867349624634},{"id":"https://openalex.org/keywords/classifier","display_name":"Classifier (UML)","score":0.44455039501190186},{"id":"https://openalex.org/keywords/small-molecule","display_name":"Small molecule","score":0.4371170997619629},{"id":"https://openalex.org/keywords/biological-system","display_name":"Biological system","score":0.4264169931411743},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.4262691140174866},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.2875295877456665},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.2220609486103058}],"concepts":[{"id":"https://openalex.org/C2781067378","wikidata":"https://www.wikidata.org/wiki/Q17027399","display_name":"Interpretability","level":2,"score":0.7096450328826904},{"id":"https://openalex.org/C103697762","wikidata":"https://www.wikidata.org/wiki/Q4112105","display_name":"Virtual screening","level":3,"score":0.5500234961509705},{"id":"https://openalex.org/C153083717","wikidata":"https://www.wikidata.org/wiki/Q6535263","display_name":"Leverage (statistics)","level":2,"score":0.5331128835678101},{"id":"https://openalex.org/C169903167","wikidata":"https://www.wikidata.org/wiki/Q3985153","display_name":"Test set","level":2,"score":0.5284654498100281},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5232716798782349},{"id":"https://openalex.org/C164126121","wikidata":"https://www.wikidata.org/wiki/Q766383","display_name":"Quantitative structure\u2013activity relationship","level":2,"score":0.5084306597709656},{"id":"https://openalex.org/C164923092","wikidata":"https://www.wikidata.org/wiki/Q3705921","display_name":"Molecular descriptor","level":3,"score":0.499661922454834},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.48818618059158325},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.45779046416282654},{"id":"https://openalex.org/C50644808","wikidata":"https://www.wikidata.org/wiki/Q192776","display_name":"Artificial neural network","level":2,"score":0.4560326635837555},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.45543867349624634},{"id":"https://openalex.org/C95623464","wikidata":"https://www.wikidata.org/wiki/Q1096149","display_name":"Classifier (UML)","level":2,"score":0.44455039501190186},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.4371170997619629},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.4264169931411743},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4262691140174866},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.2875295877456665},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.2220609486103058},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000077321","descriptor_name":"Deep Learning","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"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":"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":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D054852","descriptor_name":"Small Molecule Libraries","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.4c01472","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c01472","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:39801290","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/39801290","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:11733947","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11733947","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","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":"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.4c01472","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c01472","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/G5609074304","display_name":null,"funder_award_id":"R01DA046138","funder_id":"https://openalex.org/F4320337347","funder_display_name":"National Institute on Drug Abuse"},{"id":"https://openalex.org/G8120982525","display_name":null,"funder_award_id":"R01CA217987","funder_id":"https://openalex.org/F4320310678","funder_display_name":"Center for Strategic Scientific Initiatives, National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320310678","display_name":"Center for Strategic Scientific Initiatives, National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337347","display_name":"National Institute on Drug Abuse","ror":"https://ror.org/00fq5cm18"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":45,"referenced_works":["https://openalex.org/W2003655883","https://openalex.org/W2023567628","https://openalex.org/W2033293438","https://openalex.org/W2047245810","https://openalex.org/W2071222078","https://openalex.org/W2097310377","https://openalex.org/W2103252267","https://openalex.org/W2106100979","https://openalex.org/W2166881669","https://openalex.org/W2168480393","https://openalex.org/W2168629132","https://openalex.org/W2289619256","https://openalex.org/W2327731264","https://openalex.org/W2606462007","https://openalex.org/W2735080382","https://openalex.org/W2793396277","https://openalex.org/W2916327454","https://openalex.org/W2920724574","https://openalex.org/W2926389570","https://openalex.org/W2946617578","https://openalex.org/W2980026765","https://openalex.org/W3006560560","https://openalex.org/W3006759222","https://openalex.org/W3088011183","https://openalex.org/W3093687066","https://openalex.org/W3101609372","https://openalex.org/W3119658996","https://openalex.org/W3133900975","https://openalex.org/W3157403564","https://openalex.org/W3181755904","https://openalex.org/W3189831819","https://openalex.org/W3199584303","https://openalex.org/W3206500648","https://openalex.org/W3208006053","https://openalex.org/W4281847108","https://openalex.org/W4297179124","https://openalex.org/W4308931182","https://openalex.org/W4362677501","https://openalex.org/W4377692859","https://openalex.org/W4379599831","https://openalex.org/W4385985511","https://openalex.org/W4388197327","https://openalex.org/W4388455891","https://openalex.org/W4399327027","https://openalex.org/W4400734433"],"related_works":["https://openalex.org/W2033669961","https://openalex.org/W1518515965","https://openalex.org/W3159291941","https://openalex.org/W2063120953","https://openalex.org/W1978931025","https://openalex.org/W3149724803","https://openalex.org/W2753230657","https://openalex.org/W2165637039","https://openalex.org/W2026843845","https://openalex.org/W2080075000"],"abstract_inverted_index":{"Machine":[0],"learning":[1],"(ML)":[2],"models":[3,29,45,133,139],"now":[4],"play":[5],"a":[6,18,38,78,98,147,167,232],"crucial":[7],"role":[8],"in":[9,59,134,197,207],"predicting":[10],"properties":[11],"essential":[12],"to":[13,33,37,67,119,224],"drug":[14],"development,":[15],"such":[16],"as":[17],"drug's":[19],"logscale":[20],"acid-dissociation":[21],"constant":[22],"(p<i>K</i><sub>a</sub>).":[23],"Despite":[24],"recent":[25],"architectural":[26],"advances,":[27],"these":[28,44],"often":[30],"generalize":[31],"poorly":[32],"novel":[34,120],"compounds":[35],"due":[36],"scarcity":[39],"of":[40,70,142,211,231],"ground-truth":[41],"data.":[42],"Further,":[43],"lack":[46],"interpretability.":[47],"To":[48],"this":[49],"end,":[50],"with":[51,126,222],"deliberate":[52],"molecular":[53,144,190],"embeddings,":[54],"atomic-resolution":[55],"information":[56,188],"is":[57],"accessible":[58],"chemical":[60],"structures":[61],"by":[62,203],"observing":[63],"the":[64,106,110,140,228],"model":[65,178],"response":[66],"atomic":[68,91,161,175],"perturbations":[69],"an":[71],"input":[72],"molecule.":[73,115],"Here,":[74],"we":[75],"present":[76],"BCL-XpKa,":[77],"deep":[79],"neural":[80],"network":[81],"(DNN)-based":[82],"multitask":[83],"classifier":[84],"for":[85,101,113,200],"p<i>K</i><sub>a</sub>":[86,107,129,170],"prediction":[87,108],"that":[88,114,182],"encodes":[89],"local":[90],"environments":[92],"through":[93,160],"Mol2D":[94],"descriptors.":[95],"BCL-XpKa":[96,116,123,183,223],"outputs":[97],"discrete":[99],"distribution":[100],"each":[102],"molecule,":[103],"which":[104,165],"stores":[105],"and":[109,137,157,209,216,226],"model's":[111],"uncertainty":[112],"generalizes":[117],"well":[118],"small":[121,213],"molecules.":[122],"performs":[124],"competitively":[125],"modern":[127],"ML":[128],"predictors,":[130],"outperforms":[131],"several":[132],"generalization":[135],"tasks,":[136],"accurately":[138],"effects":[141],"common":[143],"modifications":[145],"on":[146],"molecule's":[148,168],"ionizability.":[149],"We":[150,192,218],"then":[151,219],"leverage":[152],"BCL-XpKa's":[153],"granular":[154],"descriptor":[155],"set":[156],"distribution-centered":[158],"output":[159],"sensitivity":[162],"analysis":[163],"(ASA),":[164],"decomposes":[166],"predicted":[169],"value":[171],"into":[172],"its":[173],"respective":[174],"contributions":[176],"without":[177],"retraining.":[179],"ASA":[180,221],"reveals":[181],"has":[184],"implicitly":[185],"learned":[186],"high-resolution":[187],"about":[189],"substructures.":[191],"further":[193],"demonstrate":[194],"ASA's":[195],"utility":[196],"structure":[198],"preparation":[199],"protein-ligand":[201],"docking":[202],"identifying":[204],"ionization":[205],"sites":[206],"93.2%":[208],"87.8%":[210],"complex":[212],"molecule":[214],"acids":[215],"bases.":[217],"applied":[220],"identify":[225],"optimize":[227],"physicochemical":[229],"liabilities":[230],"recently":[233],"published":[234],"KRAS-degrading":[235],"PROTAC.":[236]},"counts_by_year":[{"year":2026,"cited_by_count":2}],"updated_date":"2026-04-14T08:04:32.555800","created_date":"2025-10-10T00:00:00"}
