{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:07:11Z","timestamp":1793156831115,"version":"4.5.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":182,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM44557"],"award-info":[{"award-number":["R01 GM44557"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"D.R. Bullard-Welch Chair at Rice Univ.","award":["C-0016"],"award-info":[{"award-number":["C-0016"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["OCI-0959097"],"award-info":[{"award-number":["OCI-0959097"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,10,18]]},"abstract":"Significance<\/jats:title>\n \n Protein aggregation and amyloid formation seem to be at the heart of the pathology of multiple neurodegenerative diseases, including Alzheimer\u2019s disease.\n \n \n \n A<\/mml:mi>\n \u03b2<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n protein has long been considered one of the protein components that contributes to the pathogenesis and the progression of the disease. The concepts of energy landscape analysis established in the theory of protein folding are applied here to create a quantitative image of the aggregation energy landscape of\n \n \n \n A<\/mml:mi>\n \u03b2<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n . The resulting \u201camyloid funnel\u201d not only helps visualize the complexity of the early stages of aggregation of WT\n \n \n \n A<\/mml:mi>\n \u03b2<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n but also, predicts the effects of mutations at specific sites on aggregation behavior.\n <\/jats:p>","DOI":"10.1073\/pnas.1612362113","type":"journal-article","created":{"date-parts":[[2016,10,3]],"date-time":"2016-10-03T23:18:46Z","timestamp":1475536726000},"page":"11835-11840","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":142,"title":["Exploring the aggregation free energy landscape of the amyloid-\u03b2 protein (1\u201340)"],"prefix":"10.1073","volume":"113","author":[{"given":"Weihua","family":"Zheng","sequence":"first","affiliation":[{"name":"Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;"},{"name":"Department of Chemistry, Rice University, Houston, TX 77005;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Yeh","family":"Tsai","sequence":"additional","affiliation":[{"name":"Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;"},{"name":"Department of Chemistry, Rice University, Houston, TX 77005;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchen","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;"},{"name":"Department of Bioengineering, Rice University, Houston, TX 77005"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Wolynes","sequence":"additional","affiliation":[{"name":"Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;"},{"name":"Department of Chemistry, Rice University, Houston, TX 77005;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,10,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2101"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-2-18"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi051952q"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090379"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr500638n"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physchem-032210-103526"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physchem-040513-103738"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp212541y"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216215109"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222130110"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320483110"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401564111"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.480075"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.06.133"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711731105"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.06.021"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.04.056"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200500223"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1213151"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2014.12.007"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.10.028"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218402110"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja311963f"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja507002p"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403756101"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.06.043"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505905102"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.03.028"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.741"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.12.013"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2006.03.007"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.6b02451"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1612362113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1612362113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:25:33Z","timestamp":1649813133000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1612362113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,3]]},"references-count":33,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2016,10,18]]}},"alternative-id":["10.1073\/pnas.1612362113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1612362113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,3]]},"assertion":[{"value":"2016-10-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}