| Abstract: | Replica exchange molecular dynamics and all‐atom implicit solvent model are used to compute the structural propensities in Aβ monomers, dimers, and Aβ peptides bound to the edge of amyloid fibril. These systems represent, on an approximate level, different stages in Aβ aggregation. Aβ monomers are shown to form helical structure in the N‐terminal (residues 13 to 21). Interpeptide interactions in Aβ dimers and, especially, in the peptides bound to the fibril induce a dramatic shift in the secondary structure, from helical states toward β‐strand conformations. The sequence region 10–23 in Aβ peptide is found to form most of interpeptide interactions upon aggregation. Simulation results are tested by comparing the chemical shifts in Aβ monomers computed from simulations and obtained experimentally. Possible implications of our simulations for designing aggregation‐resistant variants of Aβ are discussed. Proteins 2009. © 2009 Wiley‐Liss, Inc. |
