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

Oligomers of amyloid-beta peptides (A beta) are formed during the early stage of the amyloidogenesis process and exhibit neurotoxicity. The oligomer formation process of A beta and even that of A beta 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 A beta fragment A beta(29-42) at the atomic level, we performed the Hamiltonian replica-permutation molecular dynamics simulation with A beta(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.