Surfactant properties of Alzheimer's A beta peptides and the mechanism of amyloid aggregation.

Impact of the Mutation A21G (Flemish Variant) on Alzheimer’s β-Amyloid Dimers by Molecular Dynamics Simulations

“…Note that A21G reduces the occurrence of this salt bridge: 32% of the time in Ab 40 -A21G and 22% of the time in Ab 42 -A21G. Similarly, the nonnative intramolecular Glu 22 -Lys 28 salt bridge is also populated in all models: 10.7%, 9.7%, 14.8%, and 15.8% for Ab 40 , Ab 42 , Ab 40 -A21G, and Ab 42 -A21G, respectively.The finding of two distinct Coulombic interactions involving Lys28 are fully consistent with recent NMR experiments of the monomer of the fragment Ab[21][22][23][24][25][26][27][28][29][30]…”

“…4 we plot the Ramachandran plot of the residue 21 from all MD-generated structures of each Ab model. We see that in Ab 40 and Ab 42 , Ala 21 explores essentially the favored (f,c) regions with a high density of residues with b-character (Fig. 4, a and c).…”

“…4, a and c). On the other hand, in Ab 40 -A21G, the Ramachandran plot of Gly 21 has a typical pattern of a glycine (Fig. 4 b), whereas in Ab 42 -A21G, the Ramachandran plot resembles that of a standard residue (Fig.…”

“…We find that only the native intermolecular contact between His 14 residues is conserved in all species. All final Ab dimers disrupt the interfaces between the strands S1 and S2, and between the strands of S2, but tend to preserve the interactions between the central hydrophobic clusters (CHC) spanning residues Leu 17 -Ala 21 , although the contacts observed are not conserved. For instance, the native intermolecular interaction between Phe 19 residues is conserved in Ab 40 , Ab 42 , and its variant, but not in Ab 40 -A21G.…”

“…However, much remains to be elucidated regarding the structure of these dimers, which are sufficient for toxicity (19,20), from both the experimental and theoretical fronts. We know, however, that Ab 40 and Ab 42 form stable dimers in solution using fluorescence resonance energy transfer (21)(22)(23). The stability of several Ab species in dimers and higher-order mers has been investigated by explicit solvent molecular dynamics (MD) simulations, including dimers of Ab 10-35 (24), hexamers of Ab (25,26), and octamers of Ab 9-40 (27).…”