Amyloid Fibril Formation Studied by Replica-Exchange Wang-Landau Simulations

As neurological diseases associated with toxic peptide aggregates emerge, the research of aggregate and fibril formation has become a prominent, yet extremely challenging problem in the biological and physical sciences. The ability to form an amyloid state has been posited as a general feature of peptide systems, which is utilized in this study using a collection of coarse-grained, generic model peptides. The H0P model¹ adds an additional neutral polarity group to the classic hydrophobic-polar (HP) model² , and is used for simplicity and efficiency. With the parallelized framework of the replica-exchange Wang-Landau (REWL)³ algorithm, we determined the density of states for all possible energies of multiple interacting model peptides. Average thermodynamic quantities are studied as the system transitions between states as dissolved peptides, disordered oligomers, and crystalline aggregate structures. Additional structural observables are calculated in a post-simulation production run, and are used to further elucidate the physical behavior during the observed transitions.


¹ G.Shi, T. Wuest, Y. W. Li, and D. P. Landau, J. Phys.: Conf. Ser. 640, 012017 (2015).
² K. A. Dill, Biochemestry 24, 1501 (1985).
³ T. Vogel, Y. W. Li, T. Wuest, and D. P. Landau, Phys. Rev. E 90, 023302 (2014).