Interaction of Aβ1−42 chains and fibrillary seeds studied by all‐atom molecular dynamics simulations

Abstract

We apply all‐atom molecular dynamics simulations to investigate interactions of amyloid beta (Aβ) fibril seeds with natively disordered Aβ chains, a process associated with the onset of Alzheimer's disease. The simulations captured attachment of Aβ chains to the fibrils suggesting an onset of both fibril's elongation and secondary nucleation, with a stronger affinity of attachment leading to elongation. Choice of fibril's model appears important for the propensity to recruit Aβ chains from solution and retain them adsorbed. Nuclear magnetic resonance‐based and cryo‐electron microscopy derived models of Aβ fibrils exhibited significant differences in the interaction with individual Aβ chains, as well as in structural and dynamical stability in solution.