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Modulation of Amyloid-β42 Conformation by Small Molecules Through Nonspecific Binding.
- Source :
-
Journal of chemical theory and computation [J Chem Theory Comput] 2019 Oct 08; Vol. 15 (10), pp. 5169-5174. Date of Electronic Publication: 2019 Sep 04. - Publication Year :
- 2019
-
Abstract
- Aggregation of amyloid-β (Aβ) peptides is a crucial step in the progression of Alzheimer's disease (AD). Identifying aggregation inhibitors against AD has been a great challenge. We report an atomistic simulation study of the inhibition mechanism of two small molecules, homotaurine and scyllo -inositol, which are AD drug candidates currently under investigation. We show that both small molecules promote a conformational change of the Aβ42 monomer toward a more collapsed phase through a nonspecific binding mechanism. This finding provides atomistic-level insights into designing potential drug candidates for future AD treatments.
- Subjects :
- Amyloid beta-Peptides chemistry
Binding Sites drug effects
Humans
Molecular Dynamics Simulation
Protein Aggregates drug effects
Protein Binding
Protein Conformation drug effects
Small Molecule Libraries chemistry
Amyloid beta-Peptides antagonists & inhibitors
Small Molecule Libraries pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1549-9626
- Volume :
- 15
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of chemical theory and computation
- Publication Type :
- Academic Journal
- Accession number :
- 31476124
- Full Text :
- https://doi.org/10.1021/acs.jctc.9b00599