{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:51:12Z","timestamp":1791445872039,"version":"4.3.3"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>\n                    Unbiased atomistic molecular dynamics simulations have been employed to examine the binding interactions between amyloid fibrils (A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (1\u201342) and tau) with various ligands: anionic pFTAA, qFTAA\u2010CN, neutral HS\u2010276, and cationic bTVBT4. The ligand\u2013fibril interactions were analyzed in a two\u2010step approach. First, an analysis of the spatial distributions of the ligands around the amyloid fibril protofilaments was carried out to identify prospective binding sites. Second, the associated ligand\u2013fibril binding energies at these sites were determined using umbrella sampling. The results reveal that pFTAA and qFTAA\u2010CN share common binding sites in both A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (1\u201342) and tau fibrils. Ligands bTVBT4 and HS\u2010276, on the other hand, are found to have different binding sites in A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (1\u201342) but share the same site in tau fibrils. An analysis of the spatial distributions of all ligand\u2013fibril pair combinations under comparable conditions shows the lowest densities when bTVBT4 interacts with A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (1\u201342) and HS\u2010276 with the tau fibril. These findings are corroborated by fluorescence costaining experiments, in which bTVBT4 and HS\u2010276 show no correlation with A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010specific and tau\u2010specific antibody markers, respectively. Further structural analysis reveals significant changes in the conformations of all ligands upon binding to the proteins compared to their conformations in aqueous solution. The binding of the anionic ligands (multiple localized negative charges) to fibrils is primarily driven by Coulombic forces, whereas the binding of the neutral HS\u2010276 and cationic bTVBT4 (single delocalized positive charge) is governed by Lennard\u2013Jones interactions. This highlights the influence of charges on binding, providing insights for the design of future ligands targeting A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (1\u201342) and tau fibrils.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202500902","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T06:56:43Z","timestamp":1777100203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Dynamics Study of the Binding of Cationic, Anionic, and Neutral Luminescent Conjugated Ligands to the Alzheimer Folds of A\n                    <i>\u03b2<\/i>\n                    (1\u201342) and Tau Fibrils"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8127-2283","authenticated-orcid":false,"given":"Yogesh","family":"Todarwal","sequence":"first","affiliation":[{"name":"Division of Theoretical Chemistry and Biology School of Engineering Sciences in Chemistry Biotechnology and Health KTH Royal Institute of Technology  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-5429","authenticated-orcid":false,"given":"Mathieu","family":"Linares","sequence":"additional","affiliation":[{"name":"PDC Center for High Performance Computing School of Electrical Engineering and Computer Sciences KTH Royal Institute of Technology  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1191-4954","authenticated-orcid":false,"given":"Patrick","family":"Norman","sequence":"additional","affiliation":[{"name":"Division of Theoretical Chemistry and Biology School of Engineering Sciences in Chemistry Biotechnology and Health KTH Royal Institute of Technology  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0235-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2016-0035"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1692-z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1066"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1791"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004643"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/1.1.103"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"581817","DOI":"10.3389\/fnagi.2020.00265","article-title":"Mechanisms of Pathogenic Tau and A\u03b2 Protein Spreading in Alzheimer's Disease","volume":"12","author":"D\u2019Errico P.","year":"2020","journal-title":"Frontiers in Aging Neuroscience"},{"key":"e_1_2_10_11_1","first-page":"748","article-title":"Relationships between Flortaucipir PET Tau Binding and Amyloid Burden, Clinical Diagnosis, Age and Cognition","volume":"140","author":"Pontecorvo M. 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