Background: Recent experiments with Amyloid β1-42 peptide have indicated that the
initial dimerization of Aβ1-42 monomers to form amyloid dimers stand out as a key event in the generation
of toxic oligomers. However, the structural characterization of Aβ1-42 dimer at the atomistic
level and the dimerization mechanism by which Aβ1-42 peptides co-aggregate still remains not clear.
Objective: In the present study, the process of Aβ17-42 peptide dimerization which is known to play
an important role in the plaque formation in Alzheimer’s disease was evaluated in terms of potential
of mean force.
Methods: The Aβ17-42 dimer was constructed using PatchDock server. We have used molecular
dynamics (MD) simulation with the umbrella sampling methodology to compute the Potential of
Mean Force for the dimerization of Aβ17-42. The global minima structure at the minimum distance
of separation was isolated from the calculated free energy profile and the interactions involved in
the formation of the dimer structure were examined. Protein-protein interfaces and the residueresidue
interactions vital for generation of the dimer complexes were also evaluated.
Results: The simulation results elucidated the interaction between the monomeric units to be governed
primarily by the hydrophobic and hydrogen bonds. The resultant Aβ17-42 dimer was found to
have an increased β-strands propensity at the hydrophobic regions encompassing the CHC region.
Furthermore, specific hydrophobic residues were found to play a vital role in the formation of the
Conclusion: From the results we may therefore conclude hydrophobic region encompassing the
CHC region to be crucial in dimerization process. The findings from this study provide detailed
information for the complex process of early events of Aβ aggregation.