{"id":"https://openalex.org/W4414011165","doi":"https://doi.org/10.1021/acs.jcim.5c00880","title":"Data-Driven Generation of Conformational Ensembles and Ternary Complexes for PROTAC and Other Chimera Systems","display_name":"Data-Driven Generation of Conformational Ensembles and Ternary Complexes for PROTAC and Other Chimera Systems","publication_year":2025,"publication_date":"2025-09-05","ids":{"openalex":"https://openalex.org/W4414011165","doi":"https://doi.org/10.1021/acs.jcim.5c00880","pmid":"https://pubmed.ncbi.nlm.nih.gov/40911906"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c00880","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00880","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.5c00880","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5041046486","display_name":"Fabio Montisci","orcid":"https://orcid.org/0000-0002-3391-3303"},"institutions":[{"id":"https://openalex.org/I4210098980","display_name":"Cambridge Crystallographic Data Centre","ror":"https://ror.org/00zbfm828","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210098980"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Fabio Montisci","raw_affiliation_strings":["Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K"],"affiliations":[{"raw_affiliation_string":"Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K","institution_ids":["https://openalex.org/I4210098980"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002297958","display_name":"Laura Friggeri","orcid":null},"institutions":[{"id":"https://openalex.org/I4210098980","display_name":"Cambridge Crystallographic Data Centre","ror":"https://ror.org/00zbfm828","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210098980"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Laura Friggeri","raw_affiliation_strings":["Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K"],"affiliations":[{"raw_affiliation_string":"Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K","institution_ids":["https://openalex.org/I4210098980"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5119547330","display_name":"Kepa K. Burusco-Goni","orcid":null},"institutions":[{"id":"https://openalex.org/I4210098980","display_name":"Cambridge Crystallographic Data Centre","ror":"https://ror.org/00zbfm828","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210098980"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Kepa K. Burusco-Goni","raw_affiliation_strings":["Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K"],"affiliations":[{"raw_affiliation_string":"Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K","institution_ids":["https://openalex.org/I4210098980"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022058667","display_name":"Patrick McCabe","orcid":"https://orcid.org/0000-0003-2538-4920"},"institutions":[{"id":"https://openalex.org/I4210098980","display_name":"Cambridge Crystallographic Data Centre","ror":"https://ror.org/00zbfm828","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210098980"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Patrick McCabe","raw_affiliation_strings":["Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K"],"affiliations":[{"raw_affiliation_string":"Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K","institution_ids":["https://openalex.org/I4210098980"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102794383","display_name":"Bojana Popovic","orcid":"https://orcid.org/0000-0002-0756-5149"},"institutions":[{"id":"https://openalex.org/I4210098980","display_name":"Cambridge Crystallographic Data Centre","ror":"https://ror.org/00zbfm828","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210098980"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Bojana Popovic","raw_affiliation_strings":["Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K"],"affiliations":[{"raw_affiliation_string":"Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K","institution_ids":["https://openalex.org/I4210098980"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5006929803","display_name":"Jason C. Cole","orcid":"https://orcid.org/0000-0002-0291-6317"},"institutions":[{"id":"https://openalex.org/I4210098980","display_name":"Cambridge Crystallographic Data Centre","ror":"https://ror.org/00zbfm828","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210098980"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Jason C. Cole","raw_affiliation_strings":["Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K"],"affiliations":[{"raw_affiliation_string":"Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K","institution_ids":["https://openalex.org/I4210098980"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":6,"corresponding_author_ids":["https://openalex.org/A5006929803"],"corresponding_institution_ids":["https://openalex.org/I4210098980"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.20577711,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"65","issue":"18","first_page":"9541","last_page":"9556"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9998999834060669,"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"}},"topics":[{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9998999834060669,"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/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.9925000071525574,"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/T12505","display_name":"Peptidase Inhibition and Analysis","score":0.991599977016449,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/chimera","display_name":"Chimera (genetics)","score":0.8782835006713867},{"id":"https://openalex.org/keywords/ternary-operation","display_name":"Ternary operation","score":0.5041042566299438},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.4184485673904419},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.30426231026649475},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.10561847686767578}],"concepts":[{"id":"https://openalex.org/C30278631","wikidata":"https://www.wikidata.org/wiki/Q281721","display_name":"Chimera (genetics)","level":3,"score":0.8782835006713867},{"id":"https://openalex.org/C64452783","wikidata":"https://www.wikidata.org/wiki/Q1524945","display_name":"Ternary operation","level":2,"score":0.5041042566299438},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4184485673904419},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.30426231026649475},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.10561847686767578},{"id":"https://openalex.org/C199360897","wikidata":"https://www.wikidata.org/wiki/Q9143","display_name":"Programming language","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000094243","descriptor_name":"Proteolysis Targeting Chimera","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D000094243","descriptor_name":"Proteolysis Targeting Chimera","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D000094243","descriptor_name":"Proteolysis Targeting Chimera","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D030562","descriptor_name":"Databases, Protein","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D030562","descriptor_name":"Databases, Protein","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D030562","descriptor_name":"Databases, Protein","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D030562","descriptor_name":"Databases, Protein","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D044767","descriptor_name":"Ubiquitin-Protein Ligases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D044767","descriptor_name":"Ubiquitin-Protein Ligases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D044767","descriptor_name":"Ubiquitin-Protein Ligases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D044767","descriptor_name":"Ubiquitin-Protein Ligases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D044767","descriptor_name":"Ubiquitin-Protein Ligases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D059748","descriptor_name":"Proteolysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D059748","descriptor_name":"Proteolysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D059748","descriptor_name":"Proteolysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D059748","descriptor_name":"Proteolysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.5c00880","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00880","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:40911906","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40911906","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:12703653","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12703653/","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.5c00880","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00880","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":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":76,"referenced_works":["https://openalex.org/W2019691413","https://openalex.org/W2026724025","https://openalex.org/W2081120309","https://openalex.org/W2090631504","https://openalex.org/W2099907934","https://openalex.org/W2101234009","https://openalex.org/W2130479394","https://openalex.org/W2151683271","https://openalex.org/W2156118208","https://openalex.org/W2170711116","https://openalex.org/W2319902168","https://openalex.org/W2510475640","https://openalex.org/W2597078857","https://openalex.org/W2600906272","https://openalex.org/W2789059526","https://openalex.org/W2803364122","https://openalex.org/W2806672448","https://openalex.org/W2883024539","https://openalex.org/W2889634813","https://openalex.org/W2906814157","https://openalex.org/W2909063104","https://openalex.org/W2913446986","https://openalex.org/W2948220248","https://openalex.org/W2949334232","https://openalex.org/W3003257820","https://openalex.org/W3011413773","https://openalex.org/W3045203019","https://openalex.org/W3088011183","https://openalex.org/W3088870471","https://openalex.org/W3090754737","https://openalex.org/W3093395956","https://openalex.org/W3100538750","https://openalex.org/W3101846323","https://openalex.org/W3130648111","https://openalex.org/W3194728321","https://openalex.org/W3203619612","https://openalex.org/W3211270181","https://openalex.org/W4205379795","https://openalex.org/W4210272978","https://openalex.org/W4224941115","https://openalex.org/W4226166856","https://openalex.org/W4281628106","https://openalex.org/W4295366450","https://openalex.org/W4302293700","https://openalex.org/W4304145060","https://openalex.org/W4307362175","https://openalex.org/W4308099893","https://openalex.org/W4309650743","https://openalex.org/W4311764032","https://openalex.org/W4318980484","https://openalex.org/W4319069190","https://openalex.org/W4319337921","https://openalex.org/W4322769035","https://openalex.org/W4381850174","https://openalex.org/W4384205999","https://openalex.org/W4386466812","https://openalex.org/W4387810293","https://openalex.org/W4388625756","https://openalex.org/W4389437568","https://openalex.org/W4389993472","https://openalex.org/W4390743751","https://openalex.org/W4391428478","https://openalex.org/W4391566815","https://openalex.org/W4392361757","https://openalex.org/W4392473833","https://openalex.org/W4392903332","https://openalex.org/W4394767272","https://openalex.org/W4399212684","https://openalex.org/W4400147969","https://openalex.org/W4400746884","https://openalex.org/W4401070507","https://openalex.org/W4401093107","https://openalex.org/W4402092619","https://openalex.org/W4402661303","https://openalex.org/W4403230026","https://openalex.org/W4403911144"],"related_works":["https://openalex.org/W2023036309","https://openalex.org/W1972863456","https://openalex.org/W2089371831","https://openalex.org/W2052399476","https://openalex.org/W2810163160","https://openalex.org/W3083970380","https://openalex.org/W2037964119","https://openalex.org/W4385077663","https://openalex.org/W4220905048","https://openalex.org/W838464343"],"abstract_inverted_index":{"We":[0],"present":[1],"the":[2,41,84,92,105,121,129,143],"protolysis-targeting":[3],"chimera":[4],"(PROTAC)":[5],"Conformer":[6,107,157],"Generator,":[7],"a":[8,55,58,148,160],"fast":[9],"and":[10,20,35,44,57,64,88,114,128,146,162,167,171,178],"knowledge-based":[11],"tool":[12],"for":[13,151,165],"generating":[14],"robust":[15,140],"conformational":[16,36],"ensembles":[17],"of":[18,46,131],"PROTACs":[19],"other":[21],"chimeric":[22],"degraders.":[23],"The":[24,73,101,155],"modeling":[25,153,166],"protocol":[26,74],"integrates":[27],"conformer":[28],"generation,":[29],"rigid-body":[30],"ternary":[31,172],"complex":[32],"(TC)":[33],"assembly,":[34],"sampling":[37],"strategies":[38],"that":[39,104,119],"address":[40],"inherent":[42],"flexibility":[43],"complexity":[45],"these":[47],"molecules.":[48],"Each":[49],"modeled":[50],"TC":[51,81,117],"is":[52],"evaluated":[53],"using":[54,77],"clash-score":[56],"surface-score,":[59],"designed":[60],"to":[61],"prioritize":[62],"sterically":[63],"geometrically":[65],"plausible":[66],"models":[67,118],"with":[68],"favorable":[69],"protein":[70,130,136],"surface":[71],"interactions.":[72],"was":[75],"validated":[76,163],"experimentally":[78],"determined":[79],"PROTAC-mediated":[80],"structures":[82,90],"from":[83,91],"Protein":[85],"Data":[86],"Bank":[87],"\"PROTAC-like\"":[89],"Cambridge":[93],"Structural":[94],"Database,":[95],"demonstrating":[96],"accuracy":[97],"across":[98],"diverse":[99],"systems.":[100],"results":[102],"show":[103],"PROTAC":[106,156],"Generator":[108,158],"can":[109],"reliably":[110],"reproduce":[111],"experimental":[112],"conformations":[113,170],"generate":[115],"simple":[116],"recapitulate":[120],"relative":[122],"orientations":[123],"between":[124],"E3":[125],"ubiquitin":[126],"ligase":[127],"interest":[132],"as":[133],"observed":[134],"in":[135],"crystal":[137],"structures.":[138],"This":[139],"validation":[141],"supports":[142],"method's":[144],"reliability":[145],"establishes":[147],"reference":[149],"framework":[150],"degrader":[152,169],"studies.":[154],"provides":[159],"structured":[161],"workflow":[164],"assessing":[168],"complexes,":[173],"enabling":[174],"rapid":[175],"ensemble":[176],"generation":[177],"downstream":[179],"integration":[180],"into":[181],"relevant":[182],"early":[183],"stage":[184],"drug":[185],"design":[186],"pipelines.":[187]},"counts_by_year":[],"updated_date":"2026-04-07T14:57:38.498316","created_date":"2025-10-10T00:00:00"}
