{"id":"https://openalex.org/W4415946047","doi":"https://doi.org/10.1021/acs.jcim.5c02338","title":"Uncovering the ATP-Dependent Activation Mechanism of NLRP3 through Integrated Computational Approaches","display_name":"Uncovering the ATP-Dependent Activation Mechanism of NLRP3 through Integrated Computational Approaches","publication_year":2025,"publication_date":"2025-11-05","ids":{"openalex":"https://openalex.org/W4415946047","doi":"https://doi.org/10.1021/acs.jcim.5c02338","pmid":"https://pubmed.ncbi.nlm.nih.gov/41194347"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c02338","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c02338","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/A5075010545","display_name":"Guanyi Li","orcid":null},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Guanyi Li","raw_affiliation_strings":["School of Pharmaceutical Sciences","Shanghai Jiao Tong University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"School of Pharmaceutical Sciences","institution_ids":[]},{"raw_affiliation_string":"Shanghai Jiao Tong University","institution_ids":["https://openalex.org/I183067930"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100375985","display_name":"Yuxuan Wang","orcid":"https://orcid.org/0000-0002-5235-6362"},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yuxuan Wang","raw_affiliation_strings":["School of Pharmaceutical Sciences","Shanghai Jiao Tong University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"School of Pharmaceutical Sciences","institution_ids":[]},{"raw_affiliation_string":"Shanghai Jiao Tong University","institution_ids":["https://openalex.org/I183067930"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100726561","display_name":"Yijing Zhang","orcid":null},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]},{"id":"https://openalex.org/I24943067","display_name":"Fudan University","ror":"https://ror.org/013q1eq08","country_code":"CN","type":"education","lineage":["https://openalex.org/I24943067"]},{"id":"https://openalex.org/I4210099446","display_name":"Huadong Hospital","ror":"https://ror.org/012wm7481","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210099446"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yijing Zhang","raw_affiliation_strings":["Department of Pharmacology, Huadong Hospital","Fudan University","School of Pharmaceutical Sciences","Shanghai Jiao Tong University","School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, Huadong Hospital","institution_ids":["https://openalex.org/I4210099446"]},{"raw_affiliation_string":"Fudan University","institution_ids":["https://openalex.org/I24943067"]},{"raw_affiliation_string":"School of Pharmaceutical Sciences","institution_ids":[]},{"raw_affiliation_string":"Shanghai Jiao Tong University","institution_ids":["https://openalex.org/I183067930"]},{"raw_affiliation_string":"School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China","institution_ids":["https://openalex.org/I183067930"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056001812","display_name":"Zhengzhong Kang","orcid":"https://orcid.org/0000-0002-7141-6244"},"institutions":[{"id":"https://openalex.org/I4210134393","display_name":"China National Chemical Engineering (China)","ror":"https://ror.org/04pwn6a43","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210134393"]},{"id":"https://openalex.org/I4210145329","display_name":"Aerospace Institute (Germany)","ror":"https://ror.org/04bpb0r34","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210145329"]}],"countries":["CN","DE"],"is_corresponding":true,"raw_author_name":"Zhengzhong Kang","raw_affiliation_strings":["Hubei Institute of Aerospace Chemotechnology","National Key Laboratory of Aerospace Chemical Power","National Key Laboratory of Aerospace Chemical Power, Hubei Institute of Aerospace Chemotechnology, Xiangyang 441003, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Institute of Aerospace Chemotechnology","institution_ids":["https://openalex.org/I4210145329"]},{"raw_affiliation_string":"National Key Laboratory of Aerospace Chemical Power","institution_ids":["https://openalex.org/I4210134393"]},{"raw_affiliation_string":"National Key Laboratory of Aerospace Chemical Power, Hubei Institute of Aerospace Chemotechnology, Xiangyang 441003, China","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5101981233","display_name":"Yaxue Zhao","orcid":null},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Yaxue Zhao","raw_affiliation_strings":["School of Pharmaceutical Sciences","Shanghai Jiao Tong University"],"raw_orcid":"https://orcid.org/0000-0002-5963-9779","affiliations":[{"raw_affiliation_string":"School of Pharmaceutical Sciences","institution_ids":[]},{"raw_affiliation_string":"Shanghai Jiao Tong University","institution_ids":["https://openalex.org/I183067930"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5056001812","https://openalex.org/A5101981233"],"corresponding_institution_ids":["https://openalex.org/I183067930","https://openalex.org/I4210134393","https://openalex.org/I4210145329"],"apc_list":null,"apc_paid":null,"fwci":0.7114,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.75990068,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":96,"max":98},"biblio":{"volume":"65","issue":"22","first_page":"12536","last_page":"12550"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11078","display_name":"Inflammasome and immune disorders","score":0.9853000044822693,"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/T11078","display_name":"Inflammasome and immune disorders","score":0.9853000044822693,"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/T11204","display_name":"Ion Channels and Receptors","score":0.0010000000474974513,"subfield":{"id":"https://openalex.org/subfields/2809","display_name":"Sensory Systems"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11337","display_name":"Tryptophan and brain disorders","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/2803","display_name":"Biological Psychiatry"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/allosteric-regulation","display_name":"Allosteric regulation","score":0.8611999750137329},{"id":"https://openalex.org/keywords/pyrin-domain","display_name":"Pyrin domain","score":0.6118000149726868},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"Molecular dynamics","score":0.5374000072479248},{"id":"https://openalex.org/keywords/conformational-change","display_name":"Conformational change","score":0.5307000279426575},{"id":"https://openalex.org/keywords/mechanism","display_name":"Mechanism (biology)","score":0.5012999773025513},{"id":"https://openalex.org/keywords/protein-structure","display_name":"Protein structure","score":0.4212999939918518},{"id":"https://openalex.org/keywords/domain","display_name":"Domain (mathematical analysis)","score":0.41690000891685486},{"id":"https://openalex.org/keywords/structural-biology","display_name":"Structural biology","score":0.3869999945163727}],"concepts":[{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.8611999750137329},{"id":"https://openalex.org/C139174496","wikidata":"https://www.wikidata.org/wiki/Q24725912","display_name":"Pyrin domain","level":4,"score":0.6118000149726868},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5501000285148621},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.5374000072479248},{"id":"https://openalex.org/C2777339483","wikidata":"https://www.wikidata.org/wiki/Q647203","display_name":"Conformational change","level":2,"score":0.5307000279426575},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.5012999773025513},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.4772999882698059},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4433000087738037},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.4212999939918518},{"id":"https://openalex.org/C36503486","wikidata":"https://www.wikidata.org/wiki/Q11235244","display_name":"Domain (mathematical analysis)","level":2,"score":0.41690000891685486},{"id":"https://openalex.org/C191120209","wikidata":"https://www.wikidata.org/wiki/Q908902","display_name":"Structural biology","level":2,"score":0.3869999945163727},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.3181999921798706},{"id":"https://openalex.org/C2989255885","wikidata":"https://www.wikidata.org/wiki/Q500256","display_name":"Molecular conformation","level":3,"score":0.31769999861717224},{"id":"https://openalex.org/C32123652","wikidata":"https://www.wikidata.org/wiki/Q2451605","display_name":"Molecular switch","level":3,"score":0.31459999084472656},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.31060001254081726},{"id":"https://openalex.org/C144292202","wikidata":"https://www.wikidata.org/wiki/Q898273","display_name":"Protein domain","level":3,"score":0.30469998717308044},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.27799999713897705},{"id":"https://openalex.org/C98763669","wikidata":"https://www.wikidata.org/wiki/Q176645","display_name":"Markov chain","level":2,"score":0.26989999413490295},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.2651999890804291},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.25130000710487366},{"id":"https://openalex.org/C2988375501","wikidata":"https://www.wikidata.org/wiki/Q847556","display_name":"Protein stability","level":2,"score":0.25110000371932983}],"mesh":[{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000378","qualifier_name":"metabolism","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":"D008390","descriptor_name":"Markov Chains","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008390","descriptor_name":"Markov Chains","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":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","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":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D058847","descriptor_name":"Inflammasomes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D058847","descriptor_name":"Inflammasomes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.5c02338","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c02338","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:41194347","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41194347","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/G751013518","display_name":null,"funder_award_id":"81603029","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":55,"referenced_works":["https://openalex.org/W1993555435","https://openalex.org/W2007662810","https://openalex.org/W2008708467","https://openalex.org/W2011301426","https://openalex.org/W2018720646","https://openalex.org/W2026692111","https://openalex.org/W2031843459","https://openalex.org/W2055484248","https://openalex.org/W2061259478","https://openalex.org/W2063021109","https://openalex.org/W2066690664","https://openalex.org/W2067174909","https://openalex.org/W2073743133","https://openalex.org/W2085213650","https://openalex.org/W2086513155","https://openalex.org/W2103945336","https://openalex.org/W2118233996","https://openalex.org/W2124042056","https://openalex.org/W2131124255","https://openalex.org/W2137444266","https://openalex.org/W2143592395","https://openalex.org/W2147988069","https://openalex.org/W2170711116","https://openalex.org/W2226825552","https://openalex.org/W2253581743","https://openalex.org/W2330799739","https://openalex.org/W2522054313","https://openalex.org/W2734356283","https://openalex.org/W2760982347","https://openalex.org/W2884445384","https://openalex.org/W2911549495","https://openalex.org/W2943293743","https://openalex.org/W2952863642","https://openalex.org/W2954782052","https://openalex.org/W2982061867","https://openalex.org/W2985449704","https://openalex.org/W2989052455","https://openalex.org/W3007908201","https://openalex.org/W3133822785","https://openalex.org/W3134632803","https://openalex.org/W3135573153","https://openalex.org/W3150635270","https://openalex.org/W3156468205","https://openalex.org/W3160057429","https://openalex.org/W3205295338","https://openalex.org/W4210338178","https://openalex.org/W4283581366","https://openalex.org/W4296773470","https://openalex.org/W4308485429","https://openalex.org/W4310157187","https://openalex.org/W4321163868","https://openalex.org/W4328108224","https://openalex.org/W4381715125","https://openalex.org/W4382239618","https://openalex.org/W4389140203"],"related_works":[],"abstract_inverted_index":{"As":[0],"a":[1,26,45,134,151,173],"central":[2],"component":[3],"of":[4,65,74,97,125,136],"NLRP3":[5,11,57,98,143,156],"inflammasome,":[6],"the":[7,50,66,75,80,95,122,142,155],"pattern":[8],"recognition":[9],"receptor":[10],"(nucleotide-binding":[12],"oligomerization":[13],"domain":[14,21,68],"(NACHT)-,":[15],"leucine-rich":[16],"repeat":[17],"(LRR)-,":[18],"and":[19,69,113,184],"pyrin":[20],"(PYD)-containing":[22],"protein":[23],"3)":[24],"plays":[25],"critical":[27],"role":[28],"in":[29],"immune":[30],"responses.":[31],"Its":[32],"abnormal":[33],"activation":[34,123,157],"is":[35],"closely":[36],"associated":[37],"with":[38,181],"various":[39],"inflammatory":[40,188],"diseases,":[41],"positioning":[42],"it":[43],"as":[44],"valuable":[46],"therapeutic":[47],"target.":[48],"During":[49],"transition":[51],"from":[52],"inactive":[53],"to":[54,120],"active":[55],"states,":[56,164],"undergoes":[58],"significant":[59,92],"conformational":[60,84,137,147,163],"changes,":[61],"including":[62,103,165],"spatial":[63],"rearrangement":[64],"NACHT":[67],"an":[70],"approximately":[71],"85.4\u00b0":[72],"rotation":[73],"WHD-HD2-LRR":[76],"module":[77],"caused":[78],"by":[79],"rearrangement.":[81],"These":[82],"substantial":[83],"transitions,":[85],"whose":[86],"molecular":[87,109],"mechanisms":[88],"remain":[89],"elusive,":[90],"present":[91],"challenges":[93],"for":[94,153,176,186],"development":[96],"inhibitors.":[99],"Here,":[100],"computational":[101],"approaches":[102],"nudged":[104],"elastic":[105],"band":[106],"(NEB)":[107],"simulations,":[108,112],"dynamics":[110],"(MD)":[111],"Markov":[114],"state":[115],"model":[116],"(MSM)":[117],"are":[118,169],"integrated":[119],"investigate":[121],"process":[124],"NLRP3.":[126],"Our":[127],"analyses":[128],"reveal":[129],"how":[130],"ATP":[131],"binding":[132],"initiates":[133],"cascade":[135],"changes":[138],"that":[139],"propagate":[140],"throughout":[141],"architecture,":[144],"driving":[145],"its":[146],"transition,":[148],"which":[149,171],"establishes":[150],"foundation":[152],"understanding":[154],"mechanism.":[158],"Meanwhile,":[159],"five":[160],"representative":[161],"metastable":[162],"three":[166],"key":[167],"intermediates,":[168],"identified,":[170],"provide":[172],"structural":[174],"basis":[175],"developing":[177],"novel":[178],"allosteric":[179],"inhibitors":[180],"improved":[182],"specificity":[183],"efficacy":[185],"NLRP3-mediated":[187],"diseases.":[189]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2025-11-25T14:43:58.451035","created_date":"2025-11-06T00:00:00"}
