In amyloid aggregation diseases soluble proteins coalesce into a wide array of undesirable structures, ranging through oligomers and prefibrillar assemblies to highly ordered amyloid fibrils and plaques. Explicit-solvent all-atom molecular dynamics (MD) simulations of amyloid aggregation have been performed for almost 20 years, revealing valuable information about this phenomenon. However, these simulations are challenged by three main problems. Firstly, current force fields modeling amyloid aggregation are insufficiently accurate. Secondly, the protein concentrations in MD simulations are usually orders of magnitude higher than those used in vitro or found in vivo, which has direct consequences on the aggregates that form. Finally, the third problem is the well-known time-scale limit of MD simulations. In this review I highlight recent approaches to overcome these three limitations.
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