☆ 4.7 Article

Modulation of Amyloid-β42 Conformation by Small Molecules Through Nonspecific Binding

JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2019)

期刊

JOURNAL OF CHEMICAL THEORY AND COMPUTATION

卷 15, 期 10, 页码 5169-5174

出版社

AMER CHEMICAL SOC

DOI: 10.1021/acs.jctc.9b00599

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Chemistry, Physical Physics, Atomic, Molecular & Chemical

资金

National Institutes of Health [GM114300]

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Reagent

摘要

Aggregation of amyloid-beta (A beta) 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 A beta 42 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.

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