Oligomer Formation of Amyloid-β(29–42) from Its Monomers Using the Hamiltonian Replica-Permutation Molecular Dynamics Simulation

Oligomers of amyloid-β peptides (Aβ) are formed during the early stage of the amyloidogenesis process and exhibit neurotoxicity. The oligomer formation process of Aβ and even that of Aβ fragments are still poorly understood, though understanding of these processes is essential for remedying Alzheimer’s disease. In order to better understand the oligomerization process of the C-terminal Aβ fragment Aβ(29–42) at the atomic level, we performed the Hamiltonian replica-permutation molecular dynamics simulation with Aβ(29–42) molecules using the explicit water solvent model. We observed that oligomers increased in size through the sequential addition of monomers to the oligomer, rather than through the assembly of small oligomers. Moreover, solvent effects played an important role in this oligomerization process.