Conformational Features of Beta-Amyloid Peptide 25–35

Abstract

Beta-amyloid peptide (Aβ) plays an important role in the mechanism of neurodegeneration in Alzheimer’s disease. A fragment of beta-Aβ(25–35) amyloid peptide with the sequence GSNKGAIIGLM is considered to be the functional domain of the amyloid Aβ peptide responsible for its neurotoxic properties and the biologically active Aβ region. Conformational analysis by the method of molecular mechanics of each peptide segment of the C-terminal part of the peptide revealed a limited number of the most probable conformations and clearly defined the forces stabilizing the structures. The results we obtained showed that the Aβ(25–35) peptide energetically preferentially adopts the a-helical conformation at the C-terminal octapeptide segment. The molecular dynamics method was used to model the intramolecular mobility pattern of the Aβ(25–35) peptide molecule. It is shown that in the low-energy conformations of the Aβ(25–35) peptide, the flexible structures in its N-terminal region were oriented differently with respect to the structures in the C-terminal part.