The amlyoid-β peptide (Aβ) is closely linked to the development of Alzheimer’s disease. Molecular dynamics (MD) simulations have become an indispensable tool for studying the behavior of this peptide at the (sub)molecular level, thereby providing insight into the molecular basis of Alzheimer’s disease. General key aspects of MD simulations are the force field used for modeling the peptide or protein and its environment, which is important for accurate modeling of the system of interest, and the length of the simulations, which determines whether or not equilibrium is reached. In this study we address these points by analyzing 30-µs MD simulations acquired for Aβ40 using seven different force fields. We assess the convergence of these simulations based on the convergence of various structural properties and of NMR and fluorescence spectroscopic observables. Moreover, we calculate Markov state models for each of the seven MD simulations, which provide an unprecedented view of the thermodynamics and kinetics of the amyloid-β peptide.
Arghadwip Paul, Suman Samantray, Marco Anteghini & Birgit Strodel