Simulating Thioflavin T and Congo Red Binding to the Fibril Structure of Amyloid-$ß$(1-42)

Abstract

Binding modes for two amyloid-β(1-42) fibril tracers, namely Thioflavin T and Congo red, were identified using unbiased all-atom molecular dynamics simulations and binding free-energy computations. Both dyes bind to primarily hydrophobic grooves on the amyloid fibril surface, perpendicular to itsβ-strands. Binding affinities computed by the MM-GBSA method are in excellent agreement with experimental values and corroborate the proposed binding modes. The binding modes can guide the rational design of novel biomarkers for amyloid fibrils