In silico identification of substrate-binding sites in type-1A α-synuclein amyloids.

ABSTRACT: Pathological amyloids associated with Parkinson and Alzheimer diseases have been shown to catalyze chemical reactions in vitro. To elucidate how small-molecule substrates interact with cross-β amyloid structures, we here employ computational approaches to investigate α-synuclein amyloid fibrils of the type-1A fold. Our initial binding pocket prediction analysis identified three distinct substrate-binding sites per protofilament, yielding a total of six sites in the dimeric type-1A amyloid structure. Molecular docking of the model phosphoester substrate para-nitrophenyl phosphate (pNPP), previously shown to be dephosphorylated by α-synuclein amyloids in vitro, was performed on the three identified sites. Docking was validated by molecular dynamics simulations for a period of 100 ns. The res

SUBMITTER: Parate S 

PROVIDER: S-EPMC12414660 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature