{"id":"https://openalex.org/W2000722154","doi":"https://doi.org/10.1021/ci500544c","title":"QM/MM Simulations of Amyloid-\u03b2 42 Degradation by IDE in the Presence and Absence of ATP","display_name":"QM/MM Simulations of Amyloid-\u03b2 42 Degradation by IDE in the Presence and Absence of ATP","publication_year":2014,"publication_date":"2014-12-24","ids":{"openalex":"https://openalex.org/W2000722154","doi":"https://doi.org/10.1021/ci500544c","mag":"2000722154","pmid":"https://pubmed.ncbi.nlm.nih.gov/25539133"},"language":"en","primary_location":{"id":"doi:10.1021/ci500544c","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ci500544c","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/A5043108004","display_name":"Carlos Cruz","orcid":"https://orcid.org/0000-0003-3490-1213"},"institutions":[{"id":"https://openalex.org/I25112270","display_name":"Universidade Federal de Pernambuco","ror":"https://ror.org/047908t24","country_code":"BR","type":"education","lineage":["https://openalex.org/I25112270"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Carlos H. B. da Cruz","raw_affiliation_strings":["Departamento\rde Qu\u00edmica\rFundamental, Universidade Federal de Pernambuco, Av. Jornalista An\u00edbal Fernandes,\rs/n, Cidade Universit\u00e1ria, Recife-PE, Brazil, 50.740-560"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departamento\rde Qu\u00edmica\rFundamental, Universidade Federal de Pernambuco, Av. Jornalista An\u00edbal Fernandes,\rs/n, Cidade Universit\u00e1ria, Recife-PE, Brazil, 50.740-560","institution_ids":["https://openalex.org/I25112270"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5060788188","display_name":"Gustavo Seabra","orcid":"https://orcid.org/0000-0002-1303-4483"},"institutions":[{"id":"https://openalex.org/I25112270","display_name":"Universidade Federal de Pernambuco","ror":"https://ror.org/047908t24","country_code":"BR","type":"education","lineage":["https://openalex.org/I25112270"]}],"countries":["BR"],"is_corresponding":true,"raw_author_name":"G. M. Seabra","raw_affiliation_strings":["Departamento\rde Qu\u00edmica\rFundamental, Universidade Federal de Pernambuco, Av. Jornalista An\u00edbal Fernandes,\rs/n, Cidade Universit\u00e1ria, Recife-PE, Brazil, 50.740-560"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departamento\rde Qu\u00edmica\rFundamental, Universidade Federal de Pernambuco, Av. Jornalista An\u00edbal Fernandes,\rs/n, Cidade Universit\u00e1ria, Recife-PE, Brazil, 50.740-560","institution_ids":["https://openalex.org/I25112270"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5060788188"],"corresponding_institution_ids":["https://openalex.org/I25112270"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":6,"citation_normalized_percentile":{"value":0.09439412,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":97},"biblio":{"volume":"55","issue":"1","first_page":"72","last_page":"83"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"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/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"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":0.9998000264167786,"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/T12254","display_name":"Machine Learning in Bioinformatics","score":0.9987999796867371,"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/degradation","display_name":"Degradation (telecommunications)","score":0.6500230431556702},{"id":"https://openalex.org/keywords/amyloid","display_name":"Amyloid (mycology)","score":0.5544735193252563},{"id":"https://openalex.org/keywords/amyloid-\u03b2","display_name":"Amyloid \u03b2","score":0.521647036075592},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5012788772583008},{"id":"https://openalex.org/keywords/amyloid-fibril","display_name":"Amyloid fibril","score":0.4474848210811615},{"id":"https://openalex.org/keywords/biophysics","display_name":"Biophysics","score":0.42928963899612427},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.3416725993156433},{"id":"https://openalex.org/keywords/medicine","display_name":"Medicine","score":0.1583707630634308},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.14051315188407898},{"id":"https://openalex.org/keywords/internal-medicine","display_name":"Internal medicine","score":0.13848760724067688}],"concepts":[{"id":"https://openalex.org/C2779679103","wikidata":"https://www.wikidata.org/wiki/Q5251805","display_name":"Degradation (telecommunications)","level":2,"score":0.6500230431556702},{"id":"https://openalex.org/C2777633098","wikidata":"https://www.wikidata.org/wiki/Q2736051","display_name":"Amyloid (mycology)","level":2,"score":0.5544735193252563},{"id":"https://openalex.org/C3019447875","wikidata":"https://www.wikidata.org/wiki/Q417667","display_name":"Amyloid \u03b2","level":3,"score":0.521647036075592},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5012788772583008},{"id":"https://openalex.org/C2994168385","wikidata":"https://www.wikidata.org/wiki/Q6740853","display_name":"Amyloid fibril","level":4,"score":0.4474848210811615},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.42928963899612427},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3416725993156433},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.1583707630634308},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.14051315188407898},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.13848760724067688},{"id":"https://openalex.org/C179104552","wikidata":"https://www.wikidata.org/wiki/Q11165","display_name":"Inorganic chemistry","level":1,"score":0.0},{"id":"https://openalex.org/C76155785","wikidata":"https://www.wikidata.org/wiki/Q418","display_name":"Telecommunications","level":1,"score":0.0},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000255","descriptor_name":"Adenosine Triphosphate","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D010446","descriptor_name":"Peptide Fragments","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D010446","descriptor_name":"Peptide Fragments","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D010446","descriptor_name":"Peptide Fragments","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D010446","descriptor_name":"Peptide Fragments","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D010446","descriptor_name":"Peptide Fragments","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D010446","descriptor_name":"Peptide Fragments","qualifier_ui":"Q000737","qualifier_name":"chemistry","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":"D011487","descriptor_name":"Protein Conformation","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":false},{"descriptor_ui":"D011789","descriptor_name":"Quantum Theory","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":false},{"descriptor_ui":"D016229","descriptor_name":"Amyloid beta-Peptides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016229","descriptor_name":"Amyloid beta-Peptides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016229","descriptor_name":"Amyloid beta-Peptides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016229","descriptor_name":"Amyloid beta-Peptides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D016229","descriptor_name":"Amyloid beta-Peptides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D016229","descriptor_name":"Amyloid beta-Peptides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","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},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/ci500544c","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ci500544c","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:25539133","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/25539133","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":[{"id":"https://metadata.un.org/sdg/7","score":0.7599999904632568,"display_name":"Affordable and clean energy"}],"awards":[{"id":"https://openalex.org/G3458936975","display_name":null,"funder_award_id":"APQ-14731.06/10","funder_id":"https://openalex.org/F4320323678","funder_display_name":"Funda\u00e7\u00e3o de Amparo \u00e0 Ci\u00eancia e Tecnologia do Estado de Pernambuco"}],"funders":[{"id":"https://openalex.org/F4320323678","display_name":"Funda\u00e7\u00e3o de Amparo \u00e0 Ci\u00eancia e Tecnologia do Estado de Pernambuco","ror":"https://ror.org/02te5rf52"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":77,"referenced_works":["https://openalex.org/W172293654","https://openalex.org/W189969322","https://openalex.org/W1567624342","https://openalex.org/W1605375472","https://openalex.org/W1693283493","https://openalex.org/W1844772668","https://openalex.org/W1963854634","https://openalex.org/W1964758803","https://openalex.org/W1967411343","https://openalex.org/W1973624175","https://openalex.org/W1980477960","https://openalex.org/W1995022799","https://openalex.org/W1995245099","https://openalex.org/W1995541462","https://openalex.org/W1997858799","https://openalex.org/W2001978042","https://openalex.org/W2004303971","https://openalex.org/W2007899228","https://openalex.org/W2010773967","https://openalex.org/W2010890708","https://openalex.org/W2015642465","https://openalex.org/W2017001642","https://openalex.org/W2020951538","https://openalex.org/W2021624791","https://openalex.org/W2022696619","https://openalex.org/W2023862001","https://openalex.org/W2024952297","https://openalex.org/W2027815611","https://openalex.org/W2030011352","https://openalex.org/W2033428109","https://openalex.org/W2033464917","https://openalex.org/W2035266068","https://openalex.org/W2038663652","https://openalex.org/W2039446440","https://openalex.org/W2040710216","https://openalex.org/W2041611469","https://openalex.org/W2042998933","https://openalex.org/W2044355358","https://openalex.org/W2045117710","https://openalex.org/W2052825194","https://openalex.org/W2053684471","https://openalex.org/W2061249617","https://openalex.org/W2061964324","https://openalex.org/W2063038722","https://openalex.org/W2063255733","https://openalex.org/W2064018465","https://openalex.org/W2067174909","https://openalex.org/W2076517751","https://openalex.org/W2082499350","https://openalex.org/W2087252609","https://openalex.org/W2087596773","https://openalex.org/W2087622424","https://openalex.org/W2088702947","https://openalex.org/W2090298030","https://openalex.org/W2091115919","https://openalex.org/W2091428128","https://openalex.org/W2092330308","https://openalex.org/W2094516606","https://openalex.org/W2095082499","https://openalex.org/W2097873358","https://openalex.org/W2100382475","https://openalex.org/W2103440561","https://openalex.org/W2105668062","https://openalex.org/W2108850637","https://openalex.org/W2111544804","https://openalex.org/W2131906067","https://openalex.org/W2133700043","https://openalex.org/W2138041386","https://openalex.org/W2138997437","https://openalex.org/W2144288821","https://openalex.org/W2153733683","https://openalex.org/W2154714625","https://openalex.org/W2155165588","https://openalex.org/W2319465148","https://openalex.org/W2885585289","https://openalex.org/W4248074746","https://openalex.org/W6630865541"],"related_works":["https://openalex.org/W2900838411","https://openalex.org/W2313742489","https://openalex.org/W4323848845","https://openalex.org/W2418228579","https://openalex.org/W2341969299","https://openalex.org/W2006116784","https://openalex.org/W2559356300","https://openalex.org/W3200937902","https://openalex.org/W2976087265","https://openalex.org/W2023973572"],"abstract_inverted_index":{"The":[0,87,98],"ability":[1],"of":[2,27,39,45,54,95,108,127,145,151],"the":[3,25,37,43,50,69,81,93,96,105,109,111,114,120,125,143,149,152,155],"insulin-degrading":[4],"enzyme":[5],"(IDE)":[6],"to":[7],"degrade":[8],"amyloid-\u03b2":[9],"42":[10],"(A\u03b242),":[11],"a":[12],"process":[13],"regulated":[14],"by":[15,47,56,92,103,158],"ATP,":[16,146],"has":[17],"been":[18],"studied":[19],"as":[20],"an":[21],"alternative":[22],"path":[23],"in":[24,49,84,124,142],"development":[26],"drugs":[28],"against":[29],"Alzheimer's":[30],"disease.":[31],"In":[32,117],"this":[33],"study,":[34],"we":[35],"calculated":[36],"potential":[38],"mean":[40],"force":[41,76],"for":[42],"degradation":[44],"A\u03b242":[46],"IDE":[48],"presence":[51,144,150],"and":[52,63,73],"absence":[53,126],"ATP":[55,128],"umbrella":[57],"sampling":[58],"with":[59],"hybrid":[60],"quantum":[61],"mechanics":[62,65],"molecular":[64],"(QM/MM)":[66],"calculations,":[67],"using":[68],"SCC-DFTB":[70],"QM":[71],"Hamiltonian":[72],"Amber":[74],"ff99SB":[75],"field.":[77],"Results":[78],"indicate":[79],"that":[80,148],"reaction":[82,156],"occurs":[83],"two":[85],"steps:":[86],"first":[88],"step":[89,100],"is":[90,101,129,136],"characterized":[91,102],"formation":[94],"intermediate.":[97],"second":[99],"breaking":[104],"peptide":[106],"bond":[107],"substrate,":[110],"latter":[112],"being":[113],"rate-determining":[115],"step.":[116],"our":[118],"simulations,":[119],"activation":[121],"energy":[122],"barrier":[123],"15":[130],"\u00b1":[131],"2":[132],"kcal":[133,138],"mol(-1),":[134],"which":[135],"7":[137],"mol(-1)":[139],"lower":[140],"than":[141],"indicating":[147],"nucleotide":[153],"decreases":[154],"rate":[157],"about":[159],"10(5)":[160],"times.":[161]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2021,"cited_by_count":1},{"year":2018,"cited_by_count":2}],"updated_date":"2026-06-16T07:32:37.131356","created_date":"2025-10-10T00:00:00"}