Difference in dimer conformation between amyloid-β(1–42) and (1–43) proteins: Replica exchange molecular dynamics simulations in water

We searched stable conformations of amyloid-β (Aβ) dimers composed of Aβ(1−42) or Aβ(1−43) protein in water by replica-exchange molecular dynamics simulations and found that Thr43 of the C-terminal of Aβ(1−43) is hydrogen bonded to Arg5 of the same monomer in the Aβ(1−43) dimer, resulting in its ring-shaped conformation, while Aβ(1−42) has no such hydrogen-bond. This conformation is expected to aggregate more easily into a compact conformation of Aβ fibrils. We also investigated the binding affinity and the specific interactions between Aβ monomers by ab initio fragment molecular orbital calculations to elucidate which Aβ residues contribute to the dimerization.