Identification of potent high-affinity secondary nucleation inhibitors of Aβ42 aggregation from an ultra-large chemical library using deep docking.

ABSTRACT: Alzheimer's disease is characterized by the aggregation of the Aβ peptide into amyloid fibrils. According to the amyloid hypothesis, pharmacologically targeting Aβ aggregation could result in disease-modifying treatments. The identification of inhibitors of Aβ aggregation, however, is complicated by complex technical challenges, which typically restrict to tens of thousands the number of compounds that can be screened in experimental aggregation assays. Here, we report a computational route to increase by 4 orders of magnitude the number of screenable compounds. We achieve this result by developing an open source pipeline version of the Deep Docking protocol, and illustrate its application to the discovery of secondary nucleation inhibitors of Aβ aggregation from an ultra-large chemical li

SUBMITTER: Brezinova M 

PROVIDER: S-EPMC12759071 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature