Interpeptide interactions induce helix to strand structural transition in Abeta peptides.

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