{"id":"https://openalex.org/W4386423764","doi":"https://doi.org/10.1021/acs.jpcb.3c04700","title":"Elucidating the Mechanisms of R248Q Mutation-Enhanced p53 Aggregation and Its Inhibition by Resveratrol","display_name":"Elucidating the Mechanisms of R248Q Mutation-Enhanced p53 Aggregation and Its Inhibition by Resveratrol","publication_year":2023,"publication_date":"2023-09-04","ids":{"openalex":"https://openalex.org/W4386423764","doi":"https://doi.org/10.1021/acs.jpcb.3c04700","pmid":"https://pubmed.ncbi.nlm.nih.gov/37665658"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jpcb.3c04700","doi":"https://doi.org/10.1021/acs.jpcb.3c04700","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jpcb.3c04700","pdf_url":null,"source":{"id":"https://openalex.org/S185621672","display_name":"The Journal of Physical Chemistry B","issn_l":"1520-5207","issn":["1520-5207","1520-6106"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-2","vabb-shw"],"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":"The Journal of Physical Chemistry B","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"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/A5100318578","display_name":"Qian Liu","orcid":"https://orcid.org/0000-0002-8265-829X","observed_orcids":["https://orcid.org/0000-0002-8265-829X"]},"institutions":[{"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/I4391768224","display_name":"State Key Laboratory of Surface Physics","ror":"https://ror.org/000nbq540","country_code":"CN","type":"facility","lineage":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Qian Liu","raw_affiliation_strings":["Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China","institution_ids":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009801711","display_name":"Le Li","orcid":"https://orcid.org/0000-0001-7504-7362","observed_orcids":["https://orcid.org/0000-0001-7504-7362"]},"institutions":[{"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/I4391768224","display_name":"State Key Laboratory of Surface Physics","ror":"https://ror.org/000nbq540","country_code":"CN","type":"facility","lineage":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Le Li","raw_affiliation_strings":["Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China","institution_ids":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013846158","display_name":"Yawei Yu","orcid":"https://orcid.org/0009-0008-5428-3241","observed_orcids":["https://orcid.org/0009-0008-5428-3241"]},"institutions":[{"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/I4391768224","display_name":"State Key Laboratory of Surface Physics","ror":"https://ror.org/000nbq540","country_code":"CN","type":"facility","lineage":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yawei Yu","raw_affiliation_strings":["Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China","institution_ids":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5007399260","display_name":"Guanghong Wei","orcid":"https://orcid.org/0000-0001-5814-3328","observed_orcids":["https://orcid.org/0000-0001-5814-3328"]},"institutions":[{"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/I4391768224","display_name":"State Key Laboratory of Surface Physics","ror":"https://ror.org/000nbq540","country_code":"CN","type":"facility","lineage":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Guanghong Wei","raw_affiliation_strings":["Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China"],"raw_orcid":"https://orcid.org/0000-0001-5814-3328","affiliations":[{"raw_affiliation_string":"Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Sciences (Ministry of Education), Fudan University, Shanghai 200438, People\u2019s Republic of China","institution_ids":["https://openalex.org/I24943067","https://openalex.org/I4391768224"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5007399260"],"corresponding_institution_ids":["https://openalex.org/I24943067","https://openalex.org/I4391768224"],"apc_list":null,"apc_paid":null,"fwci":1.4438,"has_fulltext":false,"cited_by_count":12,"citation_normalized_percentile":{"value":0.82127853,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":93,"max":99},"biblio":{"volume":"127","issue":"36","first_page":"7708","last_page":"7720"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.5996000170707703,"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"}},"topics":[{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.5996000170707703,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.3806000053882599,"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/T10934","display_name":"Heat shock proteins research","score":0.005200000014156103,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/resveratrol","display_name":"resveratrol","score":0.9879999756813049},{"id":"https://openalex.org/keywords/pterostilbene","display_name":"pterostilbene","score":0.9990000128746033},{"id":"https://openalex.org/keywords/p53-core-domain","display_name":"p53 core domain","score":0.7580000162124634},{"id":"https://openalex.org/keywords/aggregation-prone-regions","display_name":"aggregation-prone regions","score":0.9940000176429749},{"id":"https://openalex.org/keywords/small-molecule-inhibitors","display_name":"small molecule inhibitors","score":0.6819999814033508},{"id":"https://openalex.org/keywords/molecular-dynamics-simulation","display_name":"molecular dynamics simulation","score":0.503000020980835}],"concepts":[{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.8596842288970947},{"id":"https://openalex.org/C2776816829","wikidata":"https://www.wikidata.org/wiki/Q407329","display_name":"Resveratrol","level":2,"score":0.7336432933807373},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6353161334991455},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.6169567704200745},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.5889999270439148},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.5211320519447327},{"id":"https://openalex.org/C207583985","wikidata":"https://www.wikidata.org/wiki/Q128723","display_name":"Wild type","level":4,"score":0.4709008038043976},{"id":"https://openalex.org/C17077164","wikidata":"https://www.wikidata.org/wiki/Q1185869","display_name":"Inhibitory postsynaptic potential","level":2,"score":0.4415481388568878},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.42295053601264954},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.4195360243320465},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.32345062494277954},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.28070956468582153},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.13456162810325623},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.06651467084884644}],"mesh":[{"descriptor_ui":"D000077185","descriptor_name":"Resveratrol","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013267","descriptor_name":"Stilbenes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016159","descriptor_name":"Tumor Suppressor Protein p53","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jpcb.3c04700","doi":"https://doi.org/10.1021/acs.jpcb.3c04700","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jpcb.3c04700","pdf_url":null,"source":{"id":"https://openalex.org/S185621672","display_name":"The Journal of Physical Chemistry B","issn_l":"1520-5207","issn":["1520-5207","1520-6106"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-2","vabb-shw"],"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":"The Journal of Physical Chemistry B","raw_type":"journal-article"},{"id":"pmid:37665658","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37665658","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,"listed_in":[],"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":"The journal of physical chemistry. B","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.8048999905586243,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G5156286464","display_name":"ALS\u76f8\u5173\u86cb\u767d\u4f4e\u590d\u6742\u5ea6\u7ed3\u6784\u57df\u591a\u80bd\u81ea\u7ec4\u88c5\u548c\u76f8\u5206\u79bb\u7684\u5206\u5b50\u6a21\u62df\u7814\u7a76","funder_award_id":"12074079","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"},{"id":"https://openalex.org/G7198957452","display_name":null,"funder_award_id":"22ZR1406800","funder_id":"https://openalex.org/F4320309612","funder_display_name":"Natural Science Foundation of Shanghai"}],"funders":[{"id":"https://openalex.org/F4320309612","display_name":"Natural Science Foundation of Shanghai","ror":null},{"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":77,"referenced_works":["https://openalex.org/W1031578623","https://openalex.org/W1965233827","https://openalex.org/W1967058595","https://openalex.org/W1971689309","https://openalex.org/W1976499671","https://openalex.org/W1978498560","https://openalex.org/W1980396417","https://openalex.org/W1985271346","https://openalex.org/W1986076152","https://openalex.org/W1986267130","https://openalex.org/W1986503899","https://openalex.org/W1995068068","https://openalex.org/W2005918656","https://openalex.org/W2007236469","https://openalex.org/W2008708467","https://openalex.org/W2011862049","https://openalex.org/W2013136213","https://openalex.org/W2017954949","https://openalex.org/W2040740978","https://openalex.org/W2046345348","https://openalex.org/W2047596219","https://openalex.org/W2057477511","https://openalex.org/W2060513486","https://openalex.org/W2061245389","https://openalex.org/W2067174909","https://openalex.org/W2073576377","https://openalex.org/W2077000240","https://openalex.org/W2093775600","https://openalex.org/W2093865758","https://openalex.org/W2094186244","https://openalex.org/W2096276671","https://openalex.org/W2108768863","https://openalex.org/W2108966286","https://openalex.org/W2109998141","https://openalex.org/W2118233996","https://openalex.org/W2132188221","https://openalex.org/W2138107646","https://openalex.org/W2147993766","https://openalex.org/W2166269098","https://openalex.org/W2175728132","https://openalex.org/W2207474307","https://openalex.org/W2312641146","https://openalex.org/W2341866865","https://openalex.org/W2533536529","https://openalex.org/W2555870966","https://openalex.org/W2591390000","https://openalex.org/W2601855059","https://openalex.org/W2626046448","https://openalex.org/W2690481485","https://openalex.org/W2752942423","https://openalex.org/W2777126867","https://openalex.org/W2805180952","https://openalex.org/W2810340031","https://openalex.org/W2907307161","https://openalex.org/W2908811118","https://openalex.org/W2996248176","https://openalex.org/W2999554785","https://openalex.org/W3004119070","https://openalex.org/W3013763244","https://openalex.org/W3113491107","https://openalex.org/W3126550244","https://openalex.org/W3127602688","https://openalex.org/W3135012715","https://openalex.org/W3163638763","https://openalex.org/W3174122508","https://openalex.org/W3194505515","https://openalex.org/W3201356533","https://openalex.org/W3217461331","https://openalex.org/W4210383412","https://openalex.org/W4220734454","https://openalex.org/W4223918543","https://openalex.org/W4281572551","https://openalex.org/W4293865791","https://openalex.org/W4297497823","https://openalex.org/W4300688074","https://openalex.org/W4304084233","https://openalex.org/W4304889307"],"related_works":["https://openalex.org/W4400106808","https://openalex.org/W1560167384","https://openalex.org/W1572884749","https://openalex.org/W4304889307","https://openalex.org/W7161825660","https://openalex.org/W3013763244","https://openalex.org/W2810340031","https://openalex.org/W1889691760","https://openalex.org/W3201356533","https://openalex.org/W7202273802"],"abstract_inverted_index":{"Aggregation":[0],"of":[1,33,44,66,70,89,103,128,161,176,232],"p53":[2,22,34,48,72],"mutants":[3],"can":[4],"result":[5],"in":[6,123,148,155,196,204],"loss-of-function,":[7],"gain-of-function,":[8],"and":[9,24,99,126,170,185,261,274,294],"dominant-negative":[10],"effects":[11],"that":[12,56,139],"contribute":[13],"to":[14,94,179,210,218,220,235,269],"tumor":[15],"growth.":[16],"Revealing":[17],"the":[18,31,42,64,71,86,90,100,124,143,156,165,183,197,289],"mechanisms":[19],"underlying":[20],"mutation-enhanced":[21,291],"aggregation":[23,65,97,107,292],"dissecting":[25],"how":[26],"small":[27],"molecule":[28],"inhibitors":[29],"prevent":[30],"conversion":[32],"into":[35,288],"aggregation-primed":[36],"conformations":[37],"are":[38,108,200],"fundamentally":[39],"important":[40],"for":[41,47],"development":[43],"novel":[45],"therapeutics":[46],"aggregation-associated":[49],"cancers.":[50],"A":[51],"recent":[52],"experimental":[53],"study":[54,284],"shows":[55],"resveratrol":[57],"(RSV)":[58],"has":[59,214],"an":[60],"inhibitory":[61,83,101,277],"effect":[62,278],"on":[63,120,279],"hot-spot":[67],"R248Q":[68,91,121,157,198,221,233,251,280,290,299],"mutant":[69,92,199,234,281],"core":[73],"domain":[74],"(p53C),":[75],"while":[76,151],"pterostilbene":[77],"(PT)":[78],"exhibits":[79,256],"a":[80,215,257,262,270,275],"relatively":[81],"poor":[82],"efficacy.":[84],"However,":[85,254],"conformational":[87],"properties":[88],"leading":[93,178],"its":[95,236],"enhanced":[96],"propensity":[98,293],"mechanism":[102],"RSV":[104,213],"against":[105,298],"p53C":[106,122,211,222,252,272,300],"not":[109,227],"well":[110,131,190],"understood.":[111],"Herein,":[112],"we":[113],"performed":[114],"extensive":[115],"all-atom":[116],"molecular":[117],"dynamics":[118],"simulations":[119,137],"absence":[125],"presence":[127],"RSV/PT,":[129],"as":[130,132,189,191],"wild-type":[133],"(WT)":[134],"p53C.":[135,192],"Our":[136,283],"reveal":[138],"loop":[140,162,168,230],"L3,":[141],"where":[142],"mutation":[144],"resides,":[145],"remains":[146],"compact":[147],"WT":[149,205],"p53C,":[150,177,206],"it":[152],"becomes":[153],"extended":[154],"mutant.":[158],"The":[159,193],"extension":[160],"L3":[163,169,231],"weakens":[164],"interactions":[166,181],"between":[167],"two":[171],"crucial":[172],"aggregation-prone":[173],"regions":[174],"(APRs)":[175],"impaired":[180],"within":[182],"APRs":[184,195],"their":[186],"structural":[187],"destabilization":[188,242],"destabilized":[194],"more":[201],"exposed":[202],"than":[203,223],"which":[207,266],"is":[208],"conducive":[209],"aggregation.":[212,253,282,301],"higher":[216,263],"preference":[217],"bind":[219],"PT.":[224],"This":[225],"binding":[226,273],"only":[228],"stabilizes":[229],"WT-like":[237],"conformation,":[238],"preventing":[239],"L3-extension-caused":[240],"APRs'":[241,246],"but":[243],"also":[244],"reduces":[245],"solvent":[247],"exposure,":[248],"thereby":[249],"inhibiting":[250],"PT":[255],"lower":[258],"hydrogen-bonding":[259],"capability":[260],"self-association":[264],"propensity,":[265],"would":[267],"lead":[268],"reduced":[271],"weakened":[276],"provides":[285],"mechanistic":[286],"insights":[287],"RSV's":[295],"potent":[296],"inhibition":[297]},"counts_by_year":[{"year":2026,"cited_by_count":6},{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":4}],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2023-09-05T00:00:00"}