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Coarse-grained and All-atom Simulations towards the Early and Late Steps of Amyloid Fibril Formation |
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| Authors: | Mara Chiricotto Thanh Thuy Tran Phuong H. Nguyen Simone Melchionna Fabio Sterpone Philippe Derreumaux |
| Affiliation: | 1. Laboratoire de Biochimie Théorique, UPR 9080 CNRS, Université Paris Diderot, Sorbonne Paris Cité, IBPC, 13 Rue Pierre et Marie Curie, 75005 Paris, France Both authors contributed equally.;2. Laboratoire de Biochimie Théorique, UPR 9080 CNRS, Université Paris Diderot, Sorbonne Paris Cité, IBPC, 13 Rue Pierre et Marie Curie, 75005 Paris, France;3. Istituto Sistemi Complessi, Consiglio Nazionale delle Ricerche, P. le A. Moro 2, 00185 Rome, Italy |
| Abstract: | Alzheimer's disease is the most common neurodegenerative disease. Experiments and computer simulations can complement one another to provide a full and in-depth understanding of many aspects in the amyloid field at the atomistic level. Here, we review results of our coarse-grained and all-atom simulations in aqueous solution aimed at determining: 1) early aggregation steps of short linear peptides; 2) nucleation size number; 3) solution structure of the Aβ1–40/Aβ1–42 wild-type dimers; 4) impact of FAD (familial forms of Alzheimer's disease) mutations on the structure of Aβ1–40/Aβ1–42 dimers; and 5) impact of protective mutations on the structure of Aβ1–40/Aβ1–42 dimers. |
| Keywords: | Alzheimer's disease amyloid simulations computational chemistry mutations oligomerization |