{"id":"https://openalex.org/W2043580883","doi":"https://doi.org/10.1073/pnas.1209309109","title":"Equilibrium fluctuations of a single folded protein reveal a multitude of potential cryptic allosteric sites","display_name":"Equilibrium fluctuations of a single folded protein reveal a multitude of potential cryptic allosteric sites","publication_year":2012,"publication_date":"2012-07-02","ids":{"openalex":"https://openalex.org/W2043580883","doi":"https://doi.org/10.1073/pnas.1209309109","mag":"2043580883","pmid":"https://pubmed.ncbi.nlm.nih.gov/22753506","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/3406870"},"language":"en","primary_location":{"id":"doi:10.1073/pnas.1209309109","doi":"https://doi.org/10.1073/pnas.1209309109","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.1209309109","pdf_url":"https://www.pnas.org/content/pnas/109/29/11681.full.pdf","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://www.pnas.org/content/pnas/109/29/11681.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5029297375","display_name":"Gregory R. Bowman","orcid":"https://orcid.org/0000-0002-2083-4892","observed_orcids":["https://orcid.org/0000-0002-2083-4892"]},"institutions":[{"id":"https://openalex.org/I95457486","display_name":"University of California, Berkeley","ror":"https://ror.org/01an7q238","country_code":"US","type":"education","lineage":["https://openalex.org/I95457486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gregory R. Bowman","raw_affiliation_strings":["Chemistry, University of California, Berkeley, CA 94720; and","Departments of Molecular and Cell Biology, and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemistry, University of California, Berkeley, CA 94720; and","institution_ids":["https://openalex.org/I95457486"]},{"raw_affiliation_string":"Departments of Molecular and Cell Biology, and","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5030567048","display_name":"Phillip L. Geissler","orcid":"https://orcid.org/0000-0003-0268-6547","observed_orcids":["https://orcid.org/0000-0003-0268-6547"]},"institutions":[{"id":"https://openalex.org/I148283060","display_name":"Lawrence Berkeley National Laboratory","ror":"https://ror.org/02jbv0t02","country_code":"US","type":"facility","lineage":["https://openalex.org/I1330989302","https://openalex.org/I148283060","https://openalex.org/I39565521"]},{"id":"https://openalex.org/I95457486","display_name":"University of California, Berkeley","ror":"https://ror.org/01an7q238","country_code":"US","type":"education","lineage":["https://openalex.org/I95457486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Phillip L. Geissler","raw_affiliation_strings":["Chemistry, University of California, Berkeley, CA 94720; and","Physical Biosciences Division, Lawrence Berkeley National Lab, Berkeley, CA 94720"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemistry, University of California, Berkeley, CA 94720; and","institution_ids":["https://openalex.org/I95457486"]},{"raw_affiliation_string":"Physical Biosciences Division, Lawrence Berkeley National Lab, Berkeley, CA 94720","institution_ids":["https://openalex.org/I148283060"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":6.8598,"has_fulltext":true,"cited_by_count":277,"citation_normalized_percentile":{"value":0.98174578,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":99,"max":100},"biblio":{"volume":"109","issue":"29","first_page":"11681","last_page":"11686"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.9994999766349792,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":9.999999747378752e-05,"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/markov-state-models","display_name":"Markov state models","score":0.9509999752044678},{"id":"https://openalex.org/keywords/conformational-selection","display_name":"conformational selection","score":0.8659999966621399},{"id":"https://openalex.org/keywords/induced-fit","display_name":"induced fit","score":0.9750000238418579},{"id":"https://openalex.org/keywords/ligand-binding","display_name":"ligand binding","score":0.9549999833106995},{"id":"https://openalex.org/keywords/beta-lactamase","display_name":"beta-lactamase","score":0.8159999847412109},{"id":"https://openalex.org/keywords/interleukin-2","display_name":"interleukin-2","score":0.9950000047683716},{"id":"https://openalex.org/keywords/rnase-h","display_name":"RNase H","score":0.9940000176429749},{"id":"https://openalex.org/keywords/allosteric-communication","display_name":"allosteric communication","score":0.7919999957084656},{"id":"https://openalex.org/keywords/protein-conformational-sampling","display_name":"protein conformational sampling","score":0.5490000247955322}],"concepts":[{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.9498457908630371},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.5564916133880615},{"id":"https://openalex.org/C109964505","wikidata":"https://www.wikidata.org/wiki/Q3321436","display_name":"Allosteric enzyme","level":4,"score":0.5287083387374878},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5062493681907654},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.489181786775589},{"id":"https://openalex.org/C10879258","wikidata":"https://www.wikidata.org/wiki/Q76826611","display_name":"RNase P","level":4,"score":0.4669671356678009},{"id":"https://openalex.org/C2775981520","wikidata":"https://www.wikidata.org/wiki/Q17156992","display_name":"Protein dynamics","level":3,"score":0.45416954159736633},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.43384185433387756},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.4189907908439636},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.39541205763816833},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.38036778569221497},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.326737642288208},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.22798725962638855},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.13908034563064575},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.10542777180671692},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.09360188245773315},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.08220469951629639},{"id":"https://openalex.org/C159110408","wikidata":"https://www.wikidata.org/wiki/Q121176","display_name":"Nursing","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},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.0}],"mesh":[{"descriptor_ui":"D000495","descriptor_name":"Allosteric Site","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D001618","descriptor_name":"beta-Lactamases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D007376","descriptor_name":"Interleukin-2","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016914","descriptor_name":"Ribonuclease H","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D017510","descriptor_name":"Protein Folding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1073/pnas.1209309109","doi":"https://doi.org/10.1073/pnas.1209309109","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.1209309109","pdf_url":"https://www.pnas.org/content/pnas/109/29/11681.full.pdf","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:2547438","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3406870","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":null,"raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:3406870","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3406870","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"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":"Proc Natl Acad Sci U S A","raw_type":"Text"},{"id":"pmid:22753506","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/22753506","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":"Proceedings of the National Academy of Sciences of the United States of America","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1073/pnas.1209309109","doi":"https://doi.org/10.1073/pnas.1209309109","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.1209309109","pdf_url":"https://www.pnas.org/content/pnas/109/29/11681.full.pdf","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G6142181110","display_name":"Folding@Home: Simulating Folding on the Millisecond to Second Timescale","funder_award_id":"R01GM062868","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320309634","display_name":"Adolph C. and Mary Sprague Miller Institute for Basic Research in Science, University of California Berkeley","ror":null},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2043580883.pdf","grobid_xml":"https://content.openalex.org/works/W2043580883.grobid-xml"},"referenced_works_count":61,"referenced_works":["https://openalex.org/W255996521","https://openalex.org/W1898130445","https://openalex.org/W1964529071","https://openalex.org/W1966078827","https://openalex.org/W1969903391","https://openalex.org/W1979070806","https://openalex.org/W1988050069","https://openalex.org/W1996102052","https://openalex.org/W1997108831","https://openalex.org/W1998450377","https://openalex.org/W2003229373","https://openalex.org/W2003734403","https://openalex.org/W2007778981","https://openalex.org/W2017428798","https://openalex.org/W2017896410","https://openalex.org/W2022948355","https://openalex.org/W2023604759","https://openalex.org/W2027309027","https://openalex.org/W2031094493","https://openalex.org/W2031194866","https://openalex.org/W2033957087","https://openalex.org/W2037787959","https://openalex.org/W2041000185","https://openalex.org/W2041046009","https://openalex.org/W2042426030","https://openalex.org/W2043782614","https://openalex.org/W2046912614","https://openalex.org/W2047709322","https://openalex.org/W2051577656","https://openalex.org/W2053330214","https://openalex.org/W2058640773","https://openalex.org/W2061463182","https://openalex.org/W2066672837","https://openalex.org/W2066795144","https://openalex.org/W2069187578","https://openalex.org/W2070359441","https://openalex.org/W2074370114","https://openalex.org/W2075243501","https://openalex.org/W2079064092","https://openalex.org/W2082881695","https://openalex.org/W2085363913","https://openalex.org/W2092006899","https://openalex.org/W2092973995","https://openalex.org/W2096454260","https://openalex.org/W2096929343","https://openalex.org/W2105732409","https://openalex.org/W2114782816","https://openalex.org/W2116110141","https://openalex.org/W2120595908","https://openalex.org/W2123097385","https://openalex.org/W2126754172","https://openalex.org/W2131288855","https://openalex.org/W2133620840","https://openalex.org/W2140797130","https://openalex.org/W2150996942","https://openalex.org/W2155267446","https://openalex.org/W2158076215","https://openalex.org/W2170354954","https://openalex.org/W2171062007","https://openalex.org/W2313338745","https://openalex.org/W3022020637"],"related_works":["https://openalex.org/W2040286336","https://openalex.org/W2093694964","https://openalex.org/W2620864330","https://openalex.org/W2790406040","https://openalex.org/W2049131770","https://openalex.org/W4200123139","https://openalex.org/W2791506886","https://openalex.org/W4410361620","https://openalex.org/W2912891652","https://openalex.org/W2940255832"],"abstract_inverted_index":{"Cryptic":[0],"allosteric":[1,20,175,217],"sites--transient":[2],"pockets":[3,199],"in":[4,94,101,120,178,205],"a":[5,26,107,115,128,191,206,233],"folded":[6],"protein":[7],"that":[8,61,144,215,228],"are":[9],"invisible":[10],"to":[11,127,158,201],"conventional":[12],"experiments":[13],"but":[14],"can":[15,76,173],"alter":[16],"enzymatic":[17],"activity":[18],"via":[19],"communication":[21],"with":[22,138],"the":[23,36,82,95,141,179,202,238],"active":[24,203],"site--are":[25],"promising":[27],"opportunity":[28],"for":[29,117,151,165,240],"facilitating":[30],"drug":[31,40],"design":[32],"by":[33],"greatly":[34],"expanding":[35],"repertoire":[37],"of":[38,52,55,72,74,85,97,110,130,136,181,193,197,236],"available":[39],"targets.":[41],"Unfortunately,":[42],"identifying":[43],"these":[44,211],"sites":[45,80,160,218],"is":[46,146],"difficult,":[47],"typically":[48],"requiring":[49],"resource-intensive":[50],"screening":[51],"large":[53],"libraries":[54],"small":[56],"molecules.":[57],"Here,":[58],"we":[59,213],"demonstrate":[60],"Markov":[62],"state":[63],"models":[64],"built":[65],"from":[66,81],"extensive":[67,188],"computer":[68],"simulations":[69,137],"(totaling":[70],"hundreds":[71],"microseconds":[73],"dynamics)":[75],"identify":[77],"prospective":[78],"cryptic":[79,159,195,216],"equilibrium":[83],"fluctuations":[84],"three":[86],"medically":[87],"relevant":[88],"proteins--\u03b2-lactamase,":[89],"interleukin-2,":[90],"and":[91,139,161,227],"RNase":[92],"H--even":[93],"absence":[96,180],"any":[98],"ligand.":[99],"As":[100],"previous":[102],"studies,":[103],"our":[104,124,187,229],"methods":[105,230],"reveal":[106],"surprising":[108],"variety":[109],"conformations--including":[111],"bound-like":[112],"configurations--that":[113],"implies":[114],"role":[116,150],"conformational":[118],"selection":[119],"ligand":[121,142,156],"binding.":[122],"Moreover,":[123],"analyses":[125],"lead":[126],"number":[129],"unique":[131],"insights.":[132],"First,":[133],"direct":[134],"comparison":[135],"without":[140],"reveals":[143,190],"there":[145],"still":[147],"an":[148,152],"important":[149],"induced":[153],"fit":[154],"during":[155],"binding":[157],"suggests":[162],"new":[163],"conformations":[164],"docking.":[166],"Second,":[167],"correlations":[168],"between":[169],"amino":[170],"acid":[171],"sidechains":[172],"convey":[174],"signals":[176],"even":[177,221],"substantial":[182],"backbone":[183],"motions.":[184],"Most":[185],"importantly,":[186],"sampling":[189],"multitude":[192],"potential":[194],"sites--consisting":[196],"transient":[198],"coupled":[200],"site--even":[204],"single":[207],"protein.":[208],"Based":[209],"on":[210],"observations,":[212],"propose":[214],"may":[219],"be":[220,232],"more":[222],"ubiquitous":[223],"than":[224],"previously":[225],"thought":[226],"should":[231],"valuable":[234],"means":[235],"guiding":[237],"search":[239],"such":[241],"sites.":[242]},"counts_by_year":[{"year":2026,"cited_by_count":18},{"year":2025,"cited_by_count":21},{"year":2024,"cited_by_count":12},{"year":2023,"cited_by_count":21},{"year":2022,"cited_by_count":13},{"year":2021,"cited_by_count":22},{"year":2020,"cited_by_count":25},{"year":2019,"cited_by_count":17},{"year":2018,"cited_by_count":21},{"year":2017,"cited_by_count":16},{"year":2016,"cited_by_count":34},{"year":2015,"cited_by_count":25},{"year":2014,"cited_by_count":13},{"year":2013,"cited_by_count":19}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}
