{"id":"https://openalex.org/W4415009729","doi":"https://doi.org/10.1021/acs.jcim.5c01238","title":"Mechanistic Investigation of Cysteine-Targeted Covalent Inhibition of DJ-1 via MD, QM/MM, and SAPT Computations","display_name":"Mechanistic Investigation of Cysteine-Targeted Covalent Inhibition of DJ-1 via MD, QM/MM, and SAPT Computations","publication_year":2025,"publication_date":"2025-10-09","ids":{"openalex":"https://openalex.org/W4415009729","doi":"https://doi.org/10.1021/acs.jcim.5c01238","pmid":"https://pubmed.ncbi.nlm.nih.gov/41066298"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c01238","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01238","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/A5101496082","display_name":"Hao Wang","orcid":"https://orcid.org/0000-0003-1494-3774"},"institutions":[{"id":"https://openalex.org/I76130692","display_name":"Zhejiang University","ror":"https://ror.org/00a2xv884","country_code":"CN","type":"education","lineage":["https://openalex.org/I76130692"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Hao Wang","raw_affiliation_strings":["College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China","institution_ids":["https://openalex.org/I76130692"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113342131","display_name":"Ya-Min Guo","orcid":null},"institutions":[{"id":"https://openalex.org/I76130692","display_name":"Zhejiang University","ror":"https://ror.org/00a2xv884","country_code":"CN","type":"education","lineage":["https://openalex.org/I76130692"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Ya-Min Guo","raw_affiliation_strings":["College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China","institution_ids":["https://openalex.org/I76130692"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101930120","display_name":"Jinrong Yang","orcid":"https://orcid.org/0000-0002-7678-0360"},"institutions":[{"id":"https://openalex.org/I4210132079","display_name":"Hangzhou Wanxiang Polytechnic","ror":"https://ror.org/03sxnxp24","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210132079"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jin-Rong Yang","raw_affiliation_strings":["Polytechnic Institute, Zhejiang University, 269 Shixiang Rd. Hangzhou, Zhejiang 310015, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Polytechnic Institute, Zhejiang University, 269 Shixiang Rd. Hangzhou, Zhejiang 310015, China","institution_ids":["https://openalex.org/I4210132079"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101999264","display_name":"Cheng Cao","orcid":"https://orcid.org/0000-0003-0591-6803"},"institutions":[{"id":"https://openalex.org/I4210132079","display_name":"Hangzhou Wanxiang Polytechnic","ror":"https://ror.org/03sxnxp24","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210132079"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Cheng Cao","raw_affiliation_strings":["Polytechnic Institute, Zhejiang University, 269 Shixiang Rd. Hangzhou, Zhejiang 310015, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Polytechnic Institute, Zhejiang University, 269 Shixiang Rd. Hangzhou, Zhejiang 310015, China","institution_ids":["https://openalex.org/I4210132079"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025297745","display_name":"Jia-Nan Ren","orcid":null},"institutions":[{"id":"https://openalex.org/I76130692","display_name":"Zhejiang University","ror":"https://ror.org/00a2xv884","country_code":"CN","type":"education","lineage":["https://openalex.org/I76130692"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jia-Nan Ren","raw_affiliation_strings":["College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China","institution_ids":["https://openalex.org/I76130692"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088737346","display_name":"Haiqin Ye","orcid":null},"institutions":[{"id":"https://openalex.org/I76130692","display_name":"Zhejiang University","ror":"https://ror.org/00a2xv884","country_code":"CN","type":"education","lineage":["https://openalex.org/I76130692"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Hong-Yu-Xiang Ye","raw_affiliation_strings":["College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China","institution_ids":["https://openalex.org/I76130692"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5101782218","display_name":"Jian\u2010Zhong Chen","orcid":"https://orcid.org/0000-0001-7990-7876"},"institutions":[{"id":"https://openalex.org/I76130692","display_name":"Zhejiang University","ror":"https://ror.org/00a2xv884","country_code":"CN","type":"education","lineage":["https://openalex.org/I76130692"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Jian-Zhong Chen","raw_affiliation_strings":["College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China"],"raw_orcid":"https://orcid.org/0000-0001-7990-7876","affiliations":[{"raw_affiliation_string":"College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou, Zhejiang 310058, China","institution_ids":["https://openalex.org/I76130692"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5101782218"],"corresponding_institution_ids":["https://openalex.org/I76130692"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.16584006,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"65","issue":"20","first_page":"11366","last_page":"11384"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11440","display_name":"Click Chemistry and Applications","score":0.9998000264167786,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11440","display_name":"Click Chemistry and Applications","score":0.9998000264167786,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T12505","display_name":"Peptidase Inhibition and Analysis","score":0.9977999925613403,"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"}},{"id":"https://openalex.org/T13833","display_name":"Ferrocene Chemistry and Applications","score":0.996999979019165,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/covalent-bond","display_name":"Covalent bond","score":0.9041000008583069},{"id":"https://openalex.org/keywords/moiety","display_name":"Moiety","score":0.6532999873161316},{"id":"https://openalex.org/keywords/nucleophile","display_name":"Nucleophile","score":0.5468999743461609},{"id":"https://openalex.org/keywords/ligand","display_name":"Ligand (biochemistry)","score":0.4196000099182129},{"id":"https://openalex.org/keywords/nucleophilic-substitution","display_name":"Nucleophilic substitution","score":0.3968000113964081},{"id":"https://openalex.org/keywords/leaving-group","display_name":"Leaving group","score":0.39430001378059387},{"id":"https://openalex.org/keywords/binding-energy","display_name":"Binding energy","score":0.37220001220703125},{"id":"https://openalex.org/keywords/non-covalent-interactions","display_name":"Non-covalent interactions","score":0.36640000343322754},{"id":"https://openalex.org/keywords/nucleophilic-aromatic-substitution","display_name":"Nucleophilic aromatic substitution","score":0.3391000032424927}],"concepts":[{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.9041000008583069},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7684999704360962},{"id":"https://openalex.org/C2776568683","wikidata":"https://www.wikidata.org/wiki/Q23005640","display_name":"Moiety","level":2,"score":0.6532999873161316},{"id":"https://openalex.org/C178907741","wikidata":"https://www.wikidata.org/wiki/Q745930","display_name":"Nucleophile","level":3,"score":0.5468999743461609},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.4812000095844269},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.4293999969959259},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.4196000099182129},{"id":"https://openalex.org/C135731615","wikidata":"https://www.wikidata.org/wiki/Q658656","display_name":"Nucleophilic substitution","level":2,"score":0.3968000113964081},{"id":"https://openalex.org/C160964918","wikidata":"https://www.wikidata.org/wiki/Q320141","display_name":"Leaving group","level":3,"score":0.39430001378059387},{"id":"https://openalex.org/C93282013","wikidata":"https://www.wikidata.org/wiki/Q420754","display_name":"Binding energy","level":2,"score":0.37220001220703125},{"id":"https://openalex.org/C137277065","wikidata":"https://www.wikidata.org/wiki/Q2915446","display_name":"Non-covalent interactions","level":4,"score":0.36640000343322754},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.34130001068115234},{"id":"https://openalex.org/C9061509","wikidata":"https://www.wikidata.org/wiki/Q901713","display_name":"Nucleophilic aromatic substitution","level":3,"score":0.3391000032424927},{"id":"https://openalex.org/C2776910235","wikidata":"https://www.wikidata.org/wiki/Q18574","display_name":"Reactivity (psychology)","level":3,"score":0.32339999079704285},{"id":"https://openalex.org/C20803032","wikidata":"https://www.wikidata.org/wiki/Q207900","display_name":"QM/MM","level":3,"score":0.3131999969482422},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.3003999888896942},{"id":"https://openalex.org/C54516573","wikidata":"https://www.wikidata.org/wiki/Q2294","display_name":"Proton","level":2,"score":0.30000001192092896},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.2824000120162964},{"id":"https://openalex.org/C18553476","wikidata":"https://www.wikidata.org/wiki/Q1076414","display_name":"Reaction coordinate","level":2,"score":0.2791000008583069},{"id":"https://openalex.org/C122032599","wikidata":"https://www.wikidata.org/wiki/Q2914535","display_name":"Bond energy","level":3,"score":0.26919999718666077},{"id":"https://openalex.org/C3018522384","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent binding","level":3,"score":0.26759999990463257},{"id":"https://openalex.org/C108797602","wikidata":"https://www.wikidata.org/wiki/Q1059835","display_name":"Single bond","level":3,"score":0.2651999890804291},{"id":"https://openalex.org/C155860418","wikidata":"https://www.wikidata.org/wiki/Q863695","display_name":"Bond length","level":3,"score":0.25699999928474426},{"id":"https://openalex.org/C178213299","wikidata":"https://www.wikidata.org/wiki/Q44424","display_name":"Chemical bond","level":2,"score":0.2522999942302704},{"id":"https://openalex.org/C152365726","wikidata":"https://www.wikidata.org/wiki/Q1048589","display_name":"Density functional theory","level":2,"score":0.2515999972820282}],"mesh":[{"descriptor_ui":"D000071617","descriptor_name":"Protein Deglycase DJ-1","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D000071617","descriptor_name":"Protein Deglycase DJ-1","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D000071617","descriptor_name":"Protein Deglycase DJ-1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000071617","descriptor_name":"Protein Deglycase DJ-1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000071617","descriptor_name":"Protein Deglycase DJ-1","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D000071617","descriptor_name":"Protein Deglycase DJ-1","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D003545","descriptor_name":"Cysteine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D003545","descriptor_name":"Cysteine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D003545","descriptor_name":"Cysteine","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D003545","descriptor_name":"Cysteine","qualifier_ui":"Q000737","qualifier_name":"chemistry","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":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011789","descriptor_name":"Quantum Theory","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011789","descriptor_name":"Quantum Theory","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5c01238","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c01238","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:41066298","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41066298","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":[],"awards":[{"id":"https://openalex.org/G5954877771","display_name":null,"funder_award_id":"82273852","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"}],"funders":[{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":117,"referenced_works":["https://openalex.org/W88123128","https://openalex.org/W1759946603","https://openalex.org/W1793492141","https://openalex.org/W1963857586","https://openalex.org/W1968344479","https://openalex.org/W1968413329","https://openalex.org/W1971275758","https://openalex.org/W1971803965","https://openalex.org/W1973474734","https://openalex.org/W1975193651","https://openalex.org/W1975580333","https://openalex.org/W1975708211","https://openalex.org/W1976161355","https://openalex.org/W1976499671","https://openalex.org/W1978330227","https://openalex.org/W1980337077","https://openalex.org/W1982141120","https://openalex.org/W1988091937","https://openalex.org/W1988636074","https://openalex.org/W1992173555","https://openalex.org/W1993191267","https://openalex.org/W1994715640","https://openalex.org/W1995181336","https://openalex.org/W1999469282","https://openalex.org/W2000798385","https://openalex.org/W2004822259","https://openalex.org/W2008628207","https://openalex.org/W2011215428","https://openalex.org/W2026159488","https://openalex.org/W2029667189","https://openalex.org/W2033990154","https://openalex.org/W2037570317","https://openalex.org/W2037601979","https://openalex.org/W2038083805","https://openalex.org/W2038135746","https://openalex.org/W2041535798","https://openalex.org/W2044591029","https://openalex.org/W2046412723","https://openalex.org/W2049692419","https://openalex.org/W2058210956","https://openalex.org/W2058363175","https://openalex.org/W2064219132","https://openalex.org/W2067174909","https://openalex.org/W2069924395","https://openalex.org/W2070766926","https://openalex.org/W2074113799","https://openalex.org/W2078146328","https://openalex.org/W2078312014","https://openalex.org/W2080180740","https://openalex.org/W2090063868","https://openalex.org/W2092157292","https://openalex.org/W2094642658","https://openalex.org/W2094941054","https://openalex.org/W2095948536","https://openalex.org/W2096735436","https://openalex.org/W2096747776","https://openalex.org/W2104382960","https://openalex.org/W2106140689","https://openalex.org/W2111055420","https://openalex.org/W2112669910","https://openalex.org/W2112850441","https://openalex.org/W2114051156","https://openalex.org/W2118233996","https://openalex.org/W2119547517","https://openalex.org/W2124357718","https://openalex.org/W2132525235","https://openalex.org/W2133237042","https://openalex.org/W2141918542","https://openalex.org/W2144288821","https://openalex.org/W2147993766","https://openalex.org/W2148284063","https://openalex.org/W2150697053","https://openalex.org/W2158955044","https://openalex.org/W2165049467","https://openalex.org/W2166084034","https://openalex.org/W2170748127","https://openalex.org/W2327394219","https://openalex.org/W2332712348","https://openalex.org/W2404280981","https://openalex.org/W2468923062","https://openalex.org/W2473899407","https://openalex.org/W2517550655","https://openalex.org/W2580905961","https://openalex.org/W2608432272","https://openalex.org/W2613386458","https://openalex.org/W2748821508","https://openalex.org/W2770370029","https://openalex.org/W2886845898","https://openalex.org/W2951648924","https://openalex.org/W2972671588","https://openalex.org/W2982321167","https://openalex.org/W2982602983","https://openalex.org/W2999504224","https://openalex.org/W3004465863","https://openalex.org/W3009652528","https://openalex.org/W3022743377","https://openalex.org/W3038238188","https://openalex.org/W3097297264","https://openalex.org/W3105360998","https://openalex.org/W3107015841","https://openalex.org/W3140615080","https://openalex.org/W3168181021","https://openalex.org/W3171986532","https://openalex.org/W3174930543","https://openalex.org/W3195588649","https://openalex.org/W3205561180","https://openalex.org/W3215590980","https://openalex.org/W4225786175","https://openalex.org/W4280540089","https://openalex.org/W4297258617","https://openalex.org/W4298087930","https://openalex.org/W4367040931","https://openalex.org/W4376131689","https://openalex.org/W4396930324","https://openalex.org/W4401410514","https://openalex.org/W4402357074","https://openalex.org/W4403065969"],"related_works":[],"abstract_inverted_index":{"DJ-1":[0,16,96,150],"is":[1,197],"a":[2,18,78,87,106,111,122,215],"multifunctional":[3],"protein":[4,81],"implicated":[5],"in":[6,21,80,97,115,134,186,262],"cancer":[7],"and":[8,59,66,149,174],"autosomal":[9],"early":[10],"onset":[11],"Parkinson's":[12],"disease.":[13],"Cys106":[14,29,194],"of":[15,41,51,54,77,105,130,143,172,184,209,221,239,249,259,273],"plays":[17],"crucial":[19],"role":[20],"its":[22,92],"biological":[23],"functions.":[24],"The":[25,136,206],"inhibitor":[26,108],"bonded":[27],"to":[28,31,85,95,99,126,163,195,229],"needs":[30],"be":[32,83,110],"developed":[33],"with":[34,201,242],"tight":[35],"binding":[36,49,75,94,124,228,257],"for":[37,91,168,180,225,269],"the":[38,48,73,100,103,116,128,131,141,147,158,165,169,175,181,198,202,210,219,222,226,235,240,246,252,263,270],"definitive":[39],"characterization":[40],"DJ-1.":[42,135,187,230,250],"In":[43,188],"this":[44],"study,":[45],"we":[46],"investigate":[47],"mechanisms":[50,258],"two":[52],"classes":[53],"DJ-1's":[55],"covalent":[56,93,107,137,170,182,227,260],"ligands,":[57],"isatins":[58,173],"\u03b1-chloroamides,":[60],"using":[61],"MD":[62,69,152],"simulations,":[63],"QM/MM":[64,155],"calculations,":[65],"SAPT":[67,232],"analyses.":[68],"simulations":[70],"indicated":[71],"that":[72],"stable":[74,123],"process":[76],"ligand":[79],"would":[82],"beneficial":[84],"have":[86],"good":[88],"starting":[89],"point":[90],"relation":[98],"inhibition.":[101],"Moreover,":[102],"warhead":[104],"should":[109],"small":[112],"group":[113],"fitting":[114],"narrow":[117],"space":[118],"around":[119,245],"Cys106,":[120],"adopting":[121],"pose":[125],"facilitate":[127],"formation":[129,220],"C(warhead)-S(Cys106)":[132,166,223],"bond":[133,138,167,224],"can":[139],"enhance":[140],"stability":[142],"nonbonded":[144],"interactions":[145,238],"between":[146],"ligands":[148],"during":[151],"simulations.":[153],"Furthermore,":[154],"calculations":[156],"demonstrated":[157],"two-step":[159],"nucleophilic":[160,177],"addition":[161],"reaction":[162,179],"form":[164],"bindings":[171,183],"three-step":[176],"substitution":[178],"\u03b1-chloroamides":[185],"both":[189],"reactions,":[190],"proton":[191],"transfer":[192],"from":[193],"Glu18":[196],"first":[199],"step":[200],"highest":[203],"energy":[204],"barrier.":[205],"electronic":[207,237],"characteristics":[208],"phenyl":[211],"moiety":[212],"may":[213],"exert":[214],"negligible":[216],"influence":[217],"on":[218,256],"Finally,":[231],"analyses":[233],"revealed":[234],"detailed":[236],"compounds":[241],"key":[243],"residues":[244],"active":[247],"pocket":[248],"All":[251],"studies":[253],"shed":[254],"light":[255],"inhibitors":[261],"target":[264],"protein,":[265],"providing":[266],"useful":[267],"clues":[268],"drug":[271],"design":[272],"bioactive":[274],"compounds.":[275]},"counts_by_year":[],"updated_date":"2026-06-15T08:34:33.830935","created_date":"2025-10-10T00:00:00"}
