{"id":"https://openalex.org/W4399846751","doi":"https://doi.org/10.1021/acs.jcim.4c00696","title":"Correct Nucleotide Selection Is Confined at the Binding Site of Polymerase Enzymes","display_name":"Correct Nucleotide Selection Is Confined at the Binding Site of Polymerase Enzymes","publication_year":2024,"publication_date":"2024-06-20","ids":{"openalex":"https://openalex.org/W4399846751","doi":"https://doi.org/10.1021/acs.jcim.4c00696","pmid":"https://pubmed.ncbi.nlm.nih.gov/38901009"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.4c00696","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c00696","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/A5104331848","display_name":"David Ricardo Figueroa Blanco","orcid":null},"institutions":[{"id":"https://openalex.org/I30771326","display_name":"Italian Institute of Technology","ror":"https://ror.org/042t93s57","country_code":"IT","type":"facility","lineage":["https://openalex.org/I30771326"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"David Ricardo Figueroa Blanco","raw_affiliation_strings":["Laboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, Genoa 16163, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, Genoa 16163, Italy","institution_ids":["https://openalex.org/I30771326"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000266480","display_name":"Pietro Vidossich","orcid":null},"institutions":[{"id":"https://openalex.org/I30771326","display_name":"Italian Institute of Technology","ror":"https://ror.org/042t93s57","country_code":"IT","type":"facility","lineage":["https://openalex.org/I30771326"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Pietro Vidossich","raw_affiliation_strings":["Laboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, Genoa 16163, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, Genoa 16163, Italy","institution_ids":["https://openalex.org/I30771326"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5062592876","display_name":"Marco De Vivo","orcid":"https://orcid.org/0000-0003-4022-5661"},"institutions":[{"id":"https://openalex.org/I30771326","display_name":"Italian Institute of Technology","ror":"https://ror.org/042t93s57","country_code":"IT","type":"facility","lineage":["https://openalex.org/I30771326"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Marco De Vivo","raw_affiliation_strings":["Laboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, Genoa 16163, Italy"],"raw_orcid":"https://orcid.org/0000-0003-4022-5661","affiliations":[{"raw_affiliation_string":"Laboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, Genoa 16163, Italy","institution_ids":["https://openalex.org/I30771326"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5062592876"],"corresponding_institution_ids":["https://openalex.org/I30771326"],"apc_list":null,"apc_paid":null,"fwci":0.2227,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.5515488,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":91,"max":95},"biblio":{"volume":"64","issue":"13","first_page":"5285","last_page":"5294"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10432","display_name":"DNA and Nucleic Acid Chemistry","score":0.9997000098228455,"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/T10432","display_name":"DNA and Nucleic Acid Chemistry","score":0.9997000098228455,"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/T10123","display_name":"DNA Repair Mechanisms","score":0.9993000030517578,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.9929999709129333,"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/dna-polymerase","display_name":"DNA polymerase","score":0.7188776135444641},{"id":"https://openalex.org/keywords/polymerase","display_name":"Polymerase","score":0.6546692252159119},{"id":"https://openalex.org/keywords/nucleotide","display_name":"Nucleotide","score":0.6149277687072754},{"id":"https://openalex.org/keywords/dna","display_name":"DNA","score":0.5715816617012024},{"id":"https://openalex.org/keywords/dna-replication","display_name":"DNA replication","score":0.5624027848243713},{"id":"https://openalex.org/keywords/processivity","display_name":"Processivity","score":0.5180442333221436},{"id":"https://openalex.org/keywords/base-pair","display_name":"Base pair","score":0.5165252089500427},{"id":"https://openalex.org/keywords/mutant","display_name":"Mutant","score":0.4864906668663025},{"id":"https://openalex.org/keywords/dna-clamp","display_name":"DNA clamp","score":0.4543444812297821},{"id":"https://openalex.org/keywords/biophysics","display_name":"Biophysics","score":0.42137718200683594},{"id":"https://openalex.org/keywords/binding-site","display_name":"Binding site","score":0.41922321915626526},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.39166131615638733},{"id":"https://openalex.org/keywords/genetics","display_name":"Genetics","score":0.34941762685775757},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.34856978058815},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.3464186489582062},{"id":"https://openalex.org/keywords/polymerase-chain-reaction","display_name":"Polymerase chain reaction","score":0.1865968406200409},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.12113305926322937}],"concepts":[{"id":"https://openalex.org/C2756471","wikidata":"https://www.wikidata.org/wiki/Q206286","display_name":"DNA polymerase","level":3,"score":0.7188776135444641},{"id":"https://openalex.org/C82381507","wikidata":"https://www.wikidata.org/wiki/Q416878","display_name":"Polymerase","level":3,"score":0.6546692252159119},{"id":"https://openalex.org/C512185932","wikidata":"https://www.wikidata.org/wiki/Q28745","display_name":"Nucleotide","level":3,"score":0.6149277687072754},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.5715816617012024},{"id":"https://openalex.org/C73573662","wikidata":"https://www.wikidata.org/wiki/Q130996","display_name":"DNA replication","level":3,"score":0.5624027848243713},{"id":"https://openalex.org/C131140672","wikidata":"https://www.wikidata.org/wiki/Q2031164","display_name":"Processivity","level":4,"score":0.5180442333221436},{"id":"https://openalex.org/C185581394","wikidata":"https://www.wikidata.org/wiki/Q145911","display_name":"Base pair","level":3,"score":0.5165252089500427},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.4864906668663025},{"id":"https://openalex.org/C31254050","wikidata":"https://www.wikidata.org/wiki/Q22328799","display_name":"DNA clamp","level":5,"score":0.4543444812297821},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.42137718200683594},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.41922321915626526},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.39166131615638733},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.34941762685775757},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.34856978058815},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3464186489582062},{"id":"https://openalex.org/C49105822","wikidata":"https://www.wikidata.org/wiki/Q176996","display_name":"Polymerase chain reaction","level":3,"score":0.1865968406200409},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.12113305926322937},{"id":"https://openalex.org/C156719811","wikidata":"https://www.wikidata.org/wiki/Q28774","display_name":"Reverse transcriptase","level":4,"score":0.0}],"mesh":[{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D009711","descriptor_name":"Nucleotides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D009711","descriptor_name":"Nucleotides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D009711","descriptor_name":"Nucleotides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D009711","descriptor_name":"Nucleotides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D009711","descriptor_name":"Nucleotides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D009711","descriptor_name":"Nucleotides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D019951","descriptor_name":"DNA Polymerase beta","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019951","descriptor_name":"DNA Polymerase beta","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019951","descriptor_name":"DNA Polymerase beta","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019951","descriptor_name":"DNA Polymerase beta","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D019951","descriptor_name":"DNA Polymerase beta","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D019951","descriptor_name":"DNA Polymerase beta","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","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":"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.4c00696","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.4c00696","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:38901009","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/38901009","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/G8620884876","display_name":null,"funder_award_id":"IG 23679","funder_id":"https://openalex.org/F4320323054","funder_display_name":"Associazione Italiana per la Ricerca sul Cancro"}],"funders":[{"id":"https://openalex.org/F4320323054","display_name":"Associazione Italiana per la Ricerca sul Cancro","ror":"https://ror.org/02g2x7380"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":54,"referenced_works":["https://openalex.org/W1899592928","https://openalex.org/W1976499671","https://openalex.org/W1980618423","https://openalex.org/W1981225934","https://openalex.org/W1991667171","https://openalex.org/W2006662897","https://openalex.org/W2007696355","https://openalex.org/W2014118668","https://openalex.org/W2030603638","https://openalex.org/W2048020917","https://openalex.org/W2055110283","https://openalex.org/W2056390787","https://openalex.org/W2057977031","https://openalex.org/W2063318074","https://openalex.org/W2063705661","https://openalex.org/W2074512863","https://openalex.org/W2085312804","https://openalex.org/W2089138105","https://openalex.org/W2092562445","https://openalex.org/W2100380699","https://openalex.org/W2104219402","https://openalex.org/W2110089377","https://openalex.org/W2114447256","https://openalex.org/W2122223322","https://openalex.org/W2127753323","https://openalex.org/W2139022706","https://openalex.org/W2140267249","https://openalex.org/W2167423675","https://openalex.org/W2204959575","https://openalex.org/W2209595167","https://openalex.org/W2290144459","https://openalex.org/W2404280981","https://openalex.org/W2513316487","https://openalex.org/W2519392865","https://openalex.org/W2620067343","https://openalex.org/W2731784911","https://openalex.org/W2738556314","https://openalex.org/W2750714005","https://openalex.org/W2767572383","https://openalex.org/W2773541756","https://openalex.org/W2785522058","https://openalex.org/W2809762929","https://openalex.org/W2885225266","https://openalex.org/W2897651314","https://openalex.org/W2946459547","https://openalex.org/W2982067203","https://openalex.org/W3089734902","https://openalex.org/W3121702821","https://openalex.org/W3125756628","https://openalex.org/W3157572461","https://openalex.org/W3185335901","https://openalex.org/W3212329645","https://openalex.org/W4302362240","https://openalex.org/W4318614730"],"related_works":["https://openalex.org/W1996851263","https://openalex.org/W2123511727","https://openalex.org/W2000558730","https://openalex.org/W2139971497","https://openalex.org/W1993060595","https://openalex.org/W2112682448","https://openalex.org/W1982006735","https://openalex.org/W1984338426","https://openalex.org/W2075731845","https://openalex.org/W2035439427"],"abstract_inverted_index":{"DNA":[0,11,17,37],"polymerases":[1],"(Pols)":[2],"add":[3],"incoming":[4,114],"nucleotides":[5,25],"(deoxyribonucleoside":[6],"triphosphate":[7],"(dNTPs))":[8],"to":[9,27,34,64,73,99,186],"growing":[10],"strands,":[12],"a":[13,40],"crucial":[14,61],"step":[15],"for":[16],"synthesis.":[18],"The":[19],"insertion":[20],"of":[21,86,108,138,168],"correct":[22,52,93,139,170],"(vs":[23],"incorrect)":[24],"relates":[26],"Pols'":[28,32,126],"fidelity,":[29],"which":[30],"defines":[31],"ability":[33],"faithfully":[35],"replicate":[36],"strands":[38],"in":[39,83,177,192,231],"template-dependent":[41],"manner.":[42],"We":[43,180],"and":[44,51,105,134,196,213],"others":[45],"have":[46],"demonstrated":[47,148],"that":[48,75,224],"reactant":[49],"alignment":[50],"base":[53,175],"pairing":[54,176],"at":[55,79],"the":[56,76,80,84,87,113,117,130,136,151,156,188,204,220],"Pols":[57,218],"catalytic":[58,88,132],"site":[59,89,120],"are":[60,97],"structural":[62,214],"features":[63],"fidelity.":[65],"Here,":[66],"we":[67],"first":[68],"used":[69,182],"equilibrium":[70],"molecular":[71],"simulations":[72],"demonstrate":[74],"local":[77,131],"dynamics":[78],"protein-DNA":[81],"interface":[82],"proximity":[85],"is":[90,146],"different":[91],"when":[92],"vs":[94,140,172],"incorrect":[95,141,173],"dNTPs":[96],"bound":[98],"polymerase":[100],"\u03b2":[101,194],"(Pol":[102],"\u03b2).":[103],"Formation":[104],"dynamic":[106],"stability":[107],"specific":[109],"interatomic":[110],"interactions":[111],"around":[112],"nucleotide":[115],"influence":[116,135],"overall":[118],"binding":[119],"architecture.":[121],"This":[122],"explains":[123],"why":[124],"certain":[125],"mutants":[127],"can":[128],"affect":[129],"environment":[133],"selection":[137],"nucleotides.":[142],"In":[143],"particular,":[144],"this":[145],"here":[147],"by":[149,155],"analyzing":[150],"interaction":[152],"network":[153],"formed":[154],"residue":[157],"R283,":[158],"whose":[159],"mutant":[160,197],"R283A":[161],"has":[162],"an":[163],"experimentally":[164],"measured":[165],"lower":[166],"capacity":[167],"differentiating":[169],"(G:dCTP)":[171],"(G:dATP)":[174],"Pol":[178,193],"\u03b2.":[179],"also":[181,228],"alchemical":[183],"free-energy":[184],"calculations":[185],"quantify":[187],"G:dCTP":[189],"\u2192G:dATP":[190],"transformation":[191],"wild-type":[195],"R283A.":[198],"These":[199],"results":[200],"correlate":[201],"well":[202],"with":[203,216],"experimental":[205],"trend,":[206],"thus":[207],"corroborating":[208],"our":[209],"mechanistic":[210],"insights.":[211],"Sequence":[212],"comparisons":[215],"other":[217],"from":[219],"same":[221],"family":[222],"suggest":[223],"these":[225],"findings":[226],"may":[227],"be":[229],"valid":[230],"similar":[232],"enzymes.":[233]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}