A brief history of amyloid aggregation simulations

Amyloid proteins are characterized by their tendency to aggregate into amyloid fibrils, which are often associated with devastating diseases. Aggregation pathways typically involve unfolding or misfolding of monomeric proteins and formation of transient oligomers and protofibrils before the final aggregation product is formed. The conformational dynamics and polymorphic and volatile nature of these aggregation intermediates make their characterization by experimental techniques alone insufficient and also require computational approaches. Over the past 25 years, the size of simulated amyloid aggregation systems and the length of these simulations have increased significantly. These advances are discussed here. The review includes simulation approaches that model the aggregating peptides or proteins at both the all‐atom and coarse‐grained levels, use molecular dynamics simulations or Monte Carlo sampling to simulate the conformational changes, and present results for various amyloid peptides and proteins ranging from Lys‐Phe‐Phe‐Glu (KFFE) as the smallest system to Aβ$$ \mathrm{A}\upbeta $$ as an intermediate‐sized peptide to α‐synuclein. The presentation of the history of amyloid aggregation simulations concludes with a discussion of where the future of these simulations may lie. This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods Amyloid proteins tend to aggregate into oligomers, protofibrils and fibrils, which is associated with severe diseases. The study of their aggregation pathways involves computational approaches using both all‐atom and coarse‐grained models through molecular dynamics simulations or Monte Carlo sampling. The review summarizes these simulations from their beginnings to the present day.