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

Autor:	Liang C; Computational Modeling Core Facility, Institute for Applied Life Sciences (IALS) , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States., Savinov SN; Computational Modeling Core Facility, Institute for Applied Life Sciences (IALS) , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States.; Department of Biochemistry and Molecular Biology , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States., Fejzo J; Biomolecular NMR Core Facility, Institute for Applied Life Sciences (IALS) , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States., Eyles SJ; Mass Spectrometry Core Facility, Institute for Applied Life Sciences (IALS) , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States., Chen J; Department of Biochemistry and Molecular Biology , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States.; Department of Chemistry , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States.
Jazyk:	angličtina
Zdroj:	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.
DOI:	10.1021/acs.jctc.9b00599
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu