A Computational Approach to Understand the Interactions Stabilizing the Aβ1-42 Oligomers

A beta peptide aggregation is known to be an important factor in the cause of Alzheimers 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 A beta(1-42) oligomers, it is essential to understand the course of its formation and the interactions involved. But the structural dynamics of A beta(1-42) 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 A beta(1-42) peptide intermediates and the interactions stabilizing the oligomers. From the structural dynamics of A beta(1-42) oligomers, we observed the significant number of secondary structural transitions from alpha-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 proteinprotein interactions. The interaction results obtained from the PDBSum server was found to be consistent with the results obtained from the trajectory analysis