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Our approach, called metadynamic electron microscopy metainference (MEMMI), provides a characterization of the transient interactions between the fuzzy coat and the cross-\u03b2 core of the filaments. These calculations indicate that the familial AD filaments are less soluble than the sporadic AD filaments, and that the fuzzy coat contributes to solubilizing both types of filament. These results illustrate how the metainference approach can help analyze cryo-EM maps for the characterization of the properties of amyloid fibrils.<\/jats:p>","DOI":"10.1126\/sciadv.adr7008","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T14:00:44Z","timestamp":1736949644000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":18,"title":["Transient interactions between the fuzzy coat and the cross-\u03b2 core of brain-derived A\u03b242 filaments"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1902-1544","authenticated-orcid":true,"given":"Maria","family":"Milanesi","sequence":"first","affiliation":[{"name":"Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK."},{"name":"Unit of Macromolecular Interaction Analysis, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy."},{"name":"Institute for Biomedical Technologies, National Research Council (ITB-CNR), 20054 Segrate (MI), Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z. 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