Identification of high-affinity secondary nucleation inhibitors of Aβ aggregation using Deep Docking

ABSTRACT: Alzheimer's disease is characterized by aggregation of the Aβ peptide into amyloid fibrils. According to the amyloid hypothesis, pharmacologically blocking Aβ aggregation may generate disease-modifying treatments. However, inhibiting secondary nucleation, the autocatalytic process that drives the proliferation of Aβ amyloid fibrils, is technically challenging so that experimental aggregation screens are usually restricted to probing this process for only tens of thousands of molecules. To address this problem, we present a computational strategy that expands this scale by four orders of magnitude. Using an open-source implementation of the Deep Docking protocol, we virtually screened 539 million compounds for inhibitors of Aβ secondary nucleation. The pipeline prioritized 35 molecules for

SUBMITTER: Michaela Brezinova 

PROVIDER: S-SCDT-10_1038-S44320-025-00159-5 | biostudies-other |

REPOSITORIES: biostudies-other