Relaxation dynamics measure the aggregation propensity of amyloid-β and its mutants

Abstract

Atomistic molecular dynamics simulations are employed to investigate the global and segmental relaxation dynamics of the amyloid-β protein and its causative and protective mutants. Amyloid-β exhibits significant global/local dynamics that span a broad range of length and time scales due to its intrinsically disordered nature. The relaxation dynamics of the amyloid-β protein and its mutants is quantitatively correlated with its experimentally measured aggregation propensity. The protective mutant has slower relaxation dynamics, whereas the causative mutants exhibit faster global dynamics compared with that of the wild-type amyloid-β. The local dynamics of the amyloid-β protein or its mutants is governed by a complex interplay of the charge, hydrophobicity, and change in the molecular mass of the mutated residue.