Significantly different contact patterns between Aβ40 and Aβ42 monomers involving the N-terminal region

Aβ42 peptide, with two additional residues at C-terminus, aggregates much faster than Aβ40. We performed equilibrium replica-exchange molecular dynamics simulations of their monomers using our residue-specific force field. Simulated ³ J_HNHα -coupling constants agree excellently with experimental data. Aβ40 and Aβ42 have very similar local conformational features, with considerable β-strand structures in the segments: A2-H6 (A), L17-A21 (B), A30-V36 (C) of both peptides and V39-I41 (D) of Aβ42. Both peptides have abundant A-B and B-C contacts, but Aβ40 has much more contacts between A and C than Aβ42, which may retard its aggregation. Only Aβ42 has considerable A-B-C-D topology. Decreased probability of A-C contact in Aβ42 relates to the competition from C-D contact. Increased A-C contact probability may also explain the slower aggregation of A2T and A2V mutants of Aβ42.