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Since the rate of aggregation can influence neurotoxicity, finding the key factors that control this rate is of paramount importance. It was recently found that the rate of protein aggregation is related to the mechanical stability of the fibrillar structure such that the higher the mechanical stability, the faster the fibril is formed. However, this conclusion was supported by a limited dataset. In this work, we expand the previous study to a larger dataset, including the wild type of A\u03b242 peptide and its 20 mutants, the aggregation rate of which was measured experimentally. By using all-atom steered molecular dynamics (SMD) simulations, we can assess the mechanical stability of the fibril structure, which is characterized by the rupture force, pulling work, and unbinding free energy barrier. Our result confirms that mechanical stability is indeed related to the aggregation rate. Since the estimation of the aggregation rate using all-atom simulations is almost forbidden by the current computational capabilities, our result is useful for predicting it based on information obtained from fast SMD simulations for fibrils.<\/jats:p>","DOI":"10.1063\/5.0088689","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T14:05:20Z","timestamp":1657289120000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Protein aggregation rate depends on mechanical stability of fibrillar structure"],"prefix":"10.1063","volume":"157","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-8462","authenticated-orcid":false,"given":"Tran Thi Minh","family":"Thu","sequence":"first","affiliation":[{"name":"Faculty of Materials Science and Technology, University of Science-VNU HCM 1 , 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City 700000, Vietnam"},{"name":"Vietnam National University 2 , Ho Chi Minh City 700000, Vietnam"},{"name":"International Center for Research on Innovative Biobased Materials (ICRI-BioM)-International Research Agenda, Lodz University of Technology 3 , Zeromskiego 116, 90-924 Lodz, Poland"},{"name":"Institute for Computational Science and Technology 4 , SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Viet Nam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-7916","authenticated-orcid":false,"given":"Mai Suan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Computational Science and Technology 4 , SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Viet Nam"},{"name":"Institute of Physics, Polish Academy of Sciences 5 , Al. 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