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

A beta(1-40) and A beta(1-42) are the two predominant forms of amyloid beta-peptide (A beta) 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 (lie 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 A beta(1-42) has more unfolded C-terminus than A beta(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 A beta(1-42) mainly adopts beta-sheet structure, while some residues in the C-terminus of A beta(1-40) still keep initial helix structures, no beta-sheet structure is observed. The primary mechanism of different conformational behaviors of A beta(1-40) and A beta(1-42) in the solvents is analyzed and discussed based on the results of MD simulations. (C) 2009 Elsevier B.V. All rights reserved.