{"id":"https://openalex.org/W7161843822","doi":"https://doi.org/10.1093/bib/bbag231","title":"From mechanistic modeling to AI-driven design: computational strategies for targeting the \u03b3-secretase complex","display_name":"From mechanistic modeling to AI-driven design: computational strategies for targeting the \u03b3-secretase complex","publication_year":2026,"publication_date":"2026-05-01","ids":{"openalex":"https://openalex.org/W7161843822","doi":"https://doi.org/10.1093/bib/bbag231","pmid":"https://pubmed.ncbi.nlm.nih.gov/42160739"},"language":"en","primary_location":{"id":"doi:10.1093/bib/bbag231","is_oa":true,"landing_page_url":"https://doi.org/10.1093/bib/bbag231","pdf_url":null,"source":{"id":"https://openalex.org/S91767247","display_name":"Briefings in Bioinformatics","issn_l":"1467-5463","issn":["1467-5463","1477-4054"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Briefings in Bioinformatics","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1093/bib/bbag231","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5133898568","display_name":"Sutapa Das","orcid":null},"institutions":[{"id":"https://openalex.org/I164861460","display_name":"Manipal Academy of Higher Education","ror":"https://ror.org/02xzytt36","country_code":"IN","type":"education","lineage":["https://openalex.org/I164861460"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Sutapa Das","raw_affiliation_strings":["Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,","institution_ids":["https://openalex.org/I164861460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5133547853","display_name":"Shashank Rao Padubidri","orcid":null},"institutions":[{"id":"https://openalex.org/I164861460","display_name":"Manipal Academy of Higher Education","ror":"https://ror.org/02xzytt36","country_code":"IN","type":"education","lineage":["https://openalex.org/I164861460"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Shashank Rao Padubidri","raw_affiliation_strings":["Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,","institution_ids":["https://openalex.org/I164861460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5133907233","display_name":"Sreelakshmi K V","orcid":null},"institutions":[{"id":"https://openalex.org/I164861460","display_name":"Manipal Academy of Higher Education","ror":"https://ror.org/02xzytt36","country_code":"IN","type":"education","lineage":["https://openalex.org/I164861460"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Sreelakshmi K V","raw_affiliation_strings":["Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,","institution_ids":["https://openalex.org/I164861460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5133918448","display_name":"Koushik S Shetty","orcid":null},"institutions":[{"id":"https://openalex.org/I164861460","display_name":"Manipal Academy of Higher Education","ror":"https://ror.org/02xzytt36","country_code":"IN","type":"education","lineage":["https://openalex.org/I164861460"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Koushik S Shetty","raw_affiliation_strings":["Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,","institution_ids":["https://openalex.org/I164861460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5136561409","display_name":"Rutuparna Jena","orcid":null},"institutions":[{"id":"https://openalex.org/I164861460","display_name":"Manipal Academy of Higher Education","ror":"https://ror.org/02xzytt36","country_code":"IN","type":"education","lineage":["https://openalex.org/I164861460"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Rutuparna Jena","raw_affiliation_strings":["Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,","institution_ids":["https://openalex.org/I164861460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5136575276","display_name":"Himabindu K R","orcid":null},"institutions":[{"id":"https://openalex.org/I164861460","display_name":"Manipal Academy of Higher Education","ror":"https://ror.org/02xzytt36","country_code":"IN","type":"education","lineage":["https://openalex.org/I164861460"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Himabindu K R","raw_affiliation_strings":["Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,","institution_ids":["https://openalex.org/I164861460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076728587","display_name":"Budheswar Dehury","orcid":"https://orcid.org/0000-0002-9726-8454"},"institutions":[{"id":"https://openalex.org/I164861460","display_name":"Manipal Academy of Higher Education","ror":"https://ror.org/02xzytt36","country_code":"IN","type":"education","lineage":["https://openalex.org/I164861460"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Budheswar Dehury","raw_affiliation_strings":["Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,"],"raw_orcid":"https://orcid.org/0000-0002-9726-8454","affiliations":[{"raw_affiliation_string":"Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education , Manipal, Eshwar Nagar-Planetarium Complex, 576104 , Karnataka,","institution_ids":["https://openalex.org/I164861460"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5031310983","display_name":"Arun Prasad Pandurangan","orcid":"https://orcid.org/0000-0001-7168-7143"},"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"]},{"id":"https://openalex.org/I2799766170","display_name":"Papworth Hospital","ror":"https://ror.org/05mqgrb58","country_code":"GB","type":"healthcare","lineage":["https://openalex.org/I2799766170","https://openalex.org/I4210104974"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Arun Prasad Pandurangan","raw_affiliation_strings":["Department of Medicine, University of Cambridge , Cambridge Biomedical Campus, Papworth Road, Cambridge, CB2 0BB,"],"raw_orcid":"https://orcid.org/0000-0001-7168-7143","affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Cambridge , Cambridge Biomedical Campus, Papworth Road, Cambridge, CB2 0BB,","institution_ids":["https://openalex.org/I241749","https://openalex.org/I2799766170"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":3885,"currency":"USD","value_usd":3885},"apc_paid":{"value":3885,"currency":"USD","value_usd":3885},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.50235492,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"27","issue":"3","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9128000140190125,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9128000140190125,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.03290000185370445,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.008200000040233135,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/computational-model","display_name":"Computational model","score":0.7150999903678894},{"id":"https://openalex.org/keywords/drug-discovery","display_name":"Drug discovery","score":0.5674999952316284},{"id":"https://openalex.org/keywords/virtual-screening","display_name":"Virtual screening","score":0.41990000009536743},{"id":"https://openalex.org/keywords/modelling-biological-systems","display_name":"Modelling biological systems","score":0.4009000062942505},{"id":"https://openalex.org/keywords/systems-biology","display_name":"Systems biology","score":0.39100000262260437},{"id":"https://openalex.org/keywords/structural-biology","display_name":"Structural biology","score":0.35030001401901245}],"concepts":[{"id":"https://openalex.org/C66024118","wikidata":"https://www.wikidata.org/wiki/Q1122506","display_name":"Computational model","level":2,"score":0.7150999903678894},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5968999862670898},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5957000255584717},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5674999952316284},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.42640000581741333},{"id":"https://openalex.org/C103697762","wikidata":"https://www.wikidata.org/wiki/Q4112105","display_name":"Virtual screening","level":3,"score":0.41990000009536743},{"id":"https://openalex.org/C137866125","wikidata":"https://www.wikidata.org/wiki/Q4299308","display_name":"Modelling biological systems","level":3,"score":0.4009000062942505},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.39100000262260437},{"id":"https://openalex.org/C191120209","wikidata":"https://www.wikidata.org/wiki/Q908902","display_name":"Structural biology","level":2,"score":0.35030001401901245},{"id":"https://openalex.org/C39890363","wikidata":"https://www.wikidata.org/wiki/Q36108","display_name":"Generative grammar","level":2,"score":0.31029999256134033},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.2955000102519989},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2953999936580658},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.2912999987602234},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.2791000008583069},{"id":"https://openalex.org/C70587473","wikidata":"https://www.wikidata.org/wiki/Q7834111","display_name":"Transformative learning","level":2,"score":0.26010000705718994},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.2563999891281128},{"id":"https://openalex.org/C163763905","wikidata":"https://www.wikidata.org/wiki/Q17075943","display_name":"Precision medicine","level":2,"score":0.2563000023365021}],"mesh":[{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001185","descriptor_name":"Artificial Intelligence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D001185","descriptor_name":"Artificial Intelligence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D001185","descriptor_name":"Artificial Intelligence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D001185","descriptor_name":"Artificial Intelligence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D001185","descriptor_name":"Artificial Intelligence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"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":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","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":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":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000737","qualifier_name":"chemistry","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},{"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":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1093/bib/bbag231","is_oa":true,"landing_page_url":"https://doi.org/10.1093/bib/bbag231","pdf_url":null,"source":{"id":"https://openalex.org/S91767247","display_name":"Briefings in Bioinformatics","issn_l":"1467-5463","issn":["1467-5463","1477-4054"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Briefings in Bioinformatics","raw_type":"journal-article"},{"id":"pmid:42160739","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42160739","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":"Briefings in bioinformatics","raw_type":"Journal Article"},{"id":"pmh:oai:www.repository.cam.ac.uk:1810/403434","is_oa":true,"landing_page_url":"https://www.repository.cam.ac.uk/handle/1810/403434","pdf_url":"https://www.repository.cam.ac.uk/bitstreams/66ce705a-5508-4461-817b-a4b722bf1020/download","source":{"id":"https://openalex.org/S4306401777","display_name":"Apollo (University of Cambridge)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I241749","host_organization_name":"University of Cambridge","host_organization_lineage":["https://openalex.org/I241749"],"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":null,"raw_type":"Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13189169","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13189169/","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":"Brief Bioinform","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1093/bib/bbag231","is_oa":true,"landing_page_url":"https://doi.org/10.1093/bib/bbag231","pdf_url":null,"source":{"id":"https://openalex.org/S91767247","display_name":"Briefings in Bioinformatics","issn_l":"1467-5463","issn":["1467-5463","1477-4054"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Briefings in Bioinformatics","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G3613876622","display_name":"Achieving Selectivity in Space and Time with DNA Double-Strand-Break Response and Repair: Molecular Stages and Scaffolds Come with Strings Attached","funder_award_id":"200814","funder_id":"https://openalex.org/F4320311904","funder_display_name":"Wellcome Trust"},{"id":"https://openalex.org/G5478999995","display_name":"Achieving Selectivity in Space and Time with DNA Double-Strand-Break Response and Repair: Molecular Stages and Scaffolds Come with Strings Attached","funder_award_id":"200814/Z/16/Z","funder_id":"https://openalex.org/F4320311904","funder_display_name":"Wellcome Trust"}],"funders":[{"id":"https://openalex.org/F4320306227","display_name":"Arthritis National Research Foundation","ror":"https://ror.org/03abbex33"},{"id":"https://openalex.org/F4320311904","display_name":"Wellcome Trust","ror":"https://ror.org/029chgv08"},{"id":"https://openalex.org/F4320320671","display_name":"National Research Foundation","ror":"https://ror.org/05s0g1g46"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":86,"referenced_works":["https://openalex.org/W1890431460","https://openalex.org/W1928655587","https://openalex.org/W1980825524","https://openalex.org/W2029359454","https://openalex.org/W2062051632","https://openalex.org/W2323386724","https://openalex.org/W2508449322","https://openalex.org/W2514856898","https://openalex.org/W2571803537","https://openalex.org/W2623998317","https://openalex.org/W2758440030","https://openalex.org/W2906337494","https://openalex.org/W2908371579","https://openalex.org/W2912438090","https://openalex.org/W2950875286","https://openalex.org/W2952068167","https://openalex.org/W2952510283","https://openalex.org/W2953452250","https://openalex.org/W2967693091","https://openalex.org/W2980427485","https://openalex.org/W3014620327","https://openalex.org/W3025573205","https://openalex.org/W3033732543","https://openalex.org/W3036213234","https://openalex.org/W3037926339","https://openalex.org/W3080853100","https://openalex.org/W3080941805","https://openalex.org/W3087893815","https://openalex.org/W3093513572","https://openalex.org/W3094603827","https://openalex.org/W3115650052","https://openalex.org/W3130891725","https://openalex.org/W3157910233","https://openalex.org/W3166164027","https://openalex.org/W4200485596","https://openalex.org/W4206369042","https://openalex.org/W4223488106","https://openalex.org/W4223545467","https://openalex.org/W4224297388","https://openalex.org/W4252175039","https://openalex.org/W4280597922","https://openalex.org/W4281476460","https://openalex.org/W4296005585","https://openalex.org/W4307447012","https://openalex.org/W4313450550","https://openalex.org/W4320725274","https://openalex.org/W4327923869","https://openalex.org/W4365442601","https://openalex.org/W4376121341","https://openalex.org/W4377968189","https://openalex.org/W4381890246","https://openalex.org/W4385387090","https://openalex.org/W4387401786","https://openalex.org/W4387671247","https://openalex.org/W4387739920","https://openalex.org/W4388262643","https://openalex.org/W4388529501","https://openalex.org/W4388730075","https://openalex.org/W4390110459","https://openalex.org/W4390245869","https://openalex.org/W4390400981","https://openalex.org/W4391800171","https://openalex.org/W4392045516","https://openalex.org/W4392469787","https://openalex.org/W4393982116","https://openalex.org/W4394581738","https://openalex.org/W4396925744","https://openalex.org/W4399394558","https://openalex.org/W4401021414","https://openalex.org/W4401057361","https://openalex.org/W4402032238","https://openalex.org/W4403085039","https://openalex.org/W4404051067","https://openalex.org/W4405760834","https://openalex.org/W4406766095","https://openalex.org/W4407582534","https://openalex.org/W4407941091","https://openalex.org/W4407973605","https://openalex.org/W4410095152","https://openalex.org/W4410512870","https://openalex.org/W4411180023","https://openalex.org/W4411224570","https://openalex.org/W4411900408","https://openalex.org/W4412932604","https://openalex.org/W4413138685","https://openalex.org/W4416535382"],"related_works":[],"abstract_inverted_index":{"Advancements":[0],"in":[1,24,208],"computational":[2,70,75,146,199,218],"biology":[3,223],"are":[4,228],"transforming":[5],"the":[6,59,74,157,230],"study":[7],"of":[8,55,81,98,134,139,159,232,245],"complex":[9],"membrane":[10],"proteins":[11],"and":[12,28,91,101,122,130,171,205],"their":[13],"therapeutic":[14],"targeting.":[15],"The":[16],"\u03b3-secretase":[17,44,99],"complex,":[18],"a":[19,35],"quintessential":[20],"intramembrane":[21],"protease":[22],"implicated":[23],"Alzheimer's":[25],"disease":[26],"(AD)":[27],"more":[29,234],"than":[30],"150":[31],"other":[32],"substrates,":[33],"provides":[34],"powerful":[36],"exemplar":[37],"to":[38,183,224],"illustrate":[39],"this":[40,213],"transformative":[41],"shift.":[42],"Traditional":[43],"inhibitors":[45],"have":[46,94,126],"been":[47],"constrained":[48],"by":[49,68,87,110],"off-target":[50],"toxicity,":[51],"particularly":[52],"through":[53],"disruption":[54],"Notch":[56],"signaling,":[57],"underscoring":[58],"need":[60],"for":[61,179],"deeper":[62],"mechanistic":[63,152],"insights,":[64],"now":[65],"increasingly":[66,201],"enabled":[67],"modern":[69],"methodologies.":[71],"We":[72],"evaluate":[73],"strategies":[76],"driving":[77],"next-generation":[78],"drug":[79,209,226],"discovery":[80,231],"\u03b3-secretase.":[82],"Integrative":[83],"modeling":[84,147],"frameworks,":[85],"informed":[86],"cryo-electron":[88],"microscopy":[89],"(cryo-EM)":[90],"biophysical":[92],"data,":[93],"facilitated":[95],"atomic-resolution":[96],"reconstructions":[97],"dynamics":[100,106],"substrate":[102,135],"recognition.":[103],"All-atom":[104],"molecular":[105,132],"(MD)":[107],"simulations,":[108],"supported":[109],"enhanced":[111],"sampling":[112],"techniques":[113],"such":[114],"as":[115,203],"umbrella":[116],"sampling,":[117],"steered":[118],"MD,":[119,125],"replica":[120],"exchange,":[121],"Gaussian":[123],"accelerated":[124,177],"mapped":[127],"conformational":[128],"landscapes":[129],"elucidated":[131],"determinants":[133],"selectivity.":[136],"Structure-function":[137],"mapping":[138],"familial":[140],"AD":[141],"mutations":[142],"further":[143],"demonstrates":[144],"how":[145,198,216],"translates":[148],"genetic":[149],"variation":[150],"into":[151],"understanding.":[153],"Beyond":[154],"structural":[155,222],"modeling,":[156],"integration":[158],"artificial":[160],"intelligence":[161],"(AI)":[162],"including":[163],"deep":[164],"generative":[165],"models,":[166],"machine":[167],"learning-based":[168],"activity":[169],"prediction,":[170],"high-throughput":[172],"virtual":[173],"screening":[174],"has":[175],"created":[176],"pipelines":[178],"discovering":[180],"modulators":[181,236],"predicted":[182],"reduce":[184],"pathogenic":[185],"amyloid":[186],"beta":[187],"(A\u03b2)":[188],"production":[189],"while":[190],"preserving":[191],"essential":[192],"signaling":[193],"pathways.":[194],"These":[195],"approaches":[196],"demonstrate":[197],"methods":[200],"serve":[202],"predictive":[204],"design-oriented":[206],"engines":[207],"development.":[210],"Using":[211],"\u03b3-secretase,":[212],"review":[214],"highlights":[215],"state-of-the-art":[217],"techniques,":[219],"from":[220],"integrative":[221],"AI-driven":[225],"design,":[227],"reshaping":[229],"safer,":[233],"selective":[235],"with":[237],"broader":[238],"relevance":[239],"across":[240],"diseases":[241],"requiring":[242],"precise":[243],"modulation":[244],"protein":[246],"function.":[247]},"counts_by_year":[],"updated_date":"2026-08-21T09:56:20.448147","created_date":"2026-05-21T00:00:00"}
