Molecular dynamics simulation study on conformational behavior of Aβ(1-40) and Aβ(1-42) in water and methanol

Aβ(1-40) and Aβ(1-42) are the two predominant forms of amyloid β-peptide (Aβ) in the plaques found in the brains of Alzheimer's patients. They possess identical amino acid sequence except that the latter has additional two residues (Ile and Ala) at the end of C-terminus, but the latter is more prone to aggregate and neurotoxic than the former. In order to explore the reason why Aβ(1-42) has more unfolded C-terminus than Aβ(1-40) in water, we employ molecular dynamics simulation technology to investigate their different conformational behaviors in water and methanol. Results reveal that the N-terminal parts of both peptides exhibit similar structural changes, but the secondary structures of their C-terminal parts are different. In water and methanol, the C-terminus of Aβ(1-42) mainly adopts β-sheet structure, while some residues in the C-terminus of Aβ(1-40) still keep initial helix structures, no β-sheet structure is observed. The primary mechanism of different conformational behaviors of Aβ(1-40) and Aβ(1-42) in the solvents is analyzed and discussed based on the results of MD simulations.