Aβ peptide aggregation is known to be an important factor in the cause of Alzheimer’s disease (AD). Smaller oligomers, the intermediates during the process of aggregation, are known to be more neurotoxic than matured fibrils. To gain the insight into the toxicity of low molecular weight Aβ1-42 oligomers, it is essential to understand the course of its formation and the interactions involved. But the structural dynamics of Aβ1-42 oligomers at the atomistic level and the interactions holding the monomeric units in the oligomeric structures still remain elusive. In this study, using molecular dynamics simulations, we have investigated the structural dynamics of the toxic Aβ1-42 peptide intermediates and the interactions stabilizing the oligomers. From the structural dynamics of Aβ1-42 oligomers, we observed the significant number of secondary structural transitions from α-helix to random coils in some of the monomeric units. From the interaction study, we noticed the involvement of hydrophobic contacts and inter-molecular hydrogen bonds in stabilizing the oligomers. Additionally, we subjected the equilibrated structure of the oligomers in the PDBSum server to examine the protein-protein interactions. The interaction results obtained from the PDBSum server was found to be consistent with the results obtained from the trajectory analysis.
Set-up and screening of a fragment library targeting the 14-3-3 protein interface