Oxidizing a single M35 residue of A beta leads to delayed aggregation and reduced toxicity. To understand the molecular mechanism of this effect, we examined the structural and dynamical consequences of M35 oxidation. We found the mobility of the C-terminal residues of A beta 42 is greatly enhanced upon M35 oxidation. In contrast, methyl groups in the central hydrophobic cluster become less flexible. Taken together, we conclude that A beta 42(ox) undergoes A beta 40-like structural and dynamical changes, which contribute to its reduced aggregation and toxicity.