Open AccessModulation of Amyloid-β42 Conformation by Small Molecules Through Nonspecific Binding
Author(s) -
Chungwen Liang,
Sergey N. Savinov,
Jasna Fejzo,
Stephen J. Eyles,
Jianhan Chen
Publication year - 2019
Publication title -
journal of chemical theory and computation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.001
H-Index - 185
eISSN - 1549-9626
pISSN - 1549-9618
DOI - 10.1021/acs.jctc.9b00599
Subject(s) - small molecule , mechanism (biology) , chemistry , drug discovery , biophysics , amyloid (mycology) , computational biology , drug , monomer , biochemistry , biology , pharmacology , physics , inorganic chemistry , organic chemistry , quantum mechanics , polymer
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.