Abstract:
Using all-atom explicit-solvent replica-exchange molecular dynamics simulations, we explored the changes in the conformational ensemble of the Aβ monomer in various environments. In the simplest case, the Aβ monomer in water forms mostly turn and random coil conformations. We show that the anti-aggregation agent ibuprofen, the zwitterionic DMPC lipid bilayer, and even the introduction of sequence truncation (to generate the Aβ29-40 monomer) are capable of dramatically altering Aβ conformations, resulting in a stable helical structure present in the peptide’s C-terminal. For comparison, the FDDNP biomarker and other sequence truncations (e.g., the Aβ23-40 and Aβ28-40 monomers) do not exhibit a strong influence on Aβ conformations. Thus, we conclude that there is an inherent helix propensity in the Aβ C-terminal that can only be revealed by certain environments.
