title: Exploring the Alzheimer amyloid-β peptide conformational ensemble: A review of molecular dynamics approaches.
abstract: Alzheimer's disease is one of the most common dementia among elderly worldwide. There is no therapeutic drugs until now to treat effectively this disease. One main reason is due to the poorly understood mechanism of Aβ peptide aggregation, which plays a crucial role in the development of Alzheimer's disease. It remains challenging to experimentally or theoretically characterize the secondary and tertiary structures of the Aβ monomer because of its high flexibility and aggregation propensity, and its conformations that lead to the aggregation are not fully identified. In this review, we highlight various structural ensembles of Aβ peptide revealed and characterized by computational approaches in order to find converging structures of Aβ monomer. Understanding how Aβ peptide forms transiently stable structures prior to aggregation will contribute to the design of new therapeutic molecules against the Alzheimer's disease.
authors.affiliation: BioCIS, UMR CNRS 8076, LabEx LERMIT, Faculty of Pharmacy, University Paris Sud, 5 Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Linh
authors.initials: L
authors.lastname: Tran
authors.affiliation: BioCIS, UMR CNRS 8076, LabEx LERMIT, Faculty of Pharmacy, University Paris Sud, 5 Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France. Electronic address: tap.ha-duong@u-psud.fr.
authors.forename: Tâp
authors.initials: T
authors.lastname: Ha-Duong
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor
keywords: Alzheimer's disease; Aβ peptide; Coarse-grained protein models; Conformational ensembles; Enhanced sampling methods; Molecular dynamics