The 40-42 residue amyloid beta-protein (A beta) plays a central role in the pathogenesis of Alzheimer's disease (AD). Of the two main alloforms, A beta 40 and A beta 42, the longer A beta 42 is linked particularly strongly to AD. Despite the relatively small two amino acid length difference in primary structure, in vitro studies demonstrate that A beta 40 and A beta 42 oligomerize through distinct pathways, Recently, a discrete molecular dynamics (DMD) approach combined with a four-bead protein model recapitulated the differences in A beta 40 and A beta 42 oligomerization and led to structural predictions amenable to in vitro testing. Here, the same DMD approach is applied to elucidate folding of A beta 40, A beta 42, and two mutants, [G22]A beta 40 and [G22]A beta 42, which cause a familial ("Arctic") form of AD. The implicit solvent in the DMD approach is modeled by amino acid-specific hydropathic and electrostatic interactions. The strengths of these effective interactions are chosen to best fit the temperature dependence of the average beta-strand content in A beta 42 monomer, as determined using circular dichroism (CD) spectroscopy. In agreement with these CD data, we show that at physiological temperatures, the average P-strand content in both alloforms increases with temperature. Our results predict that the average beta-strand propensity should decrease in both alloforms at temperatures higher than similar to 370 K. At physiological temperatures, both A beta 40 and A beta 42 adopt a collapsed-coil conformation with several short beta-strands and a small (<1%) amount of alpha-helical structure. At slightly above physiological temperature, folded A beta 42 monomers display larger amounts of beta-strand than do A beta 40 monomers. At increased temperatures, more extended conformations with a higher amount of beta-strand (less than or similar to 30%) structure are observed. In both alloforms, a beta-hairpin at A21-A30 is a central folding region. We observe three additional folded regions: structure 1, a beta-hairpin at V36-A42 that exists in A beta 42 but not in A beta 40; structure 2, a beta-hairpin at R5-H13 in A beta 42 but not in A beta 40; and structure 3, a beta-strand A2-F4 in A beta 40 but not A beta 42. At physiological temperatures, the Arctic mutation, E22G, disrupts contacts in the A21-A30 region of both [G22]A beta peptides, resulting in a less stable main folding region relative to the wild type peptides. The Arctic mutation induces a significant structural change at the N-terminus of [G22]A beta 40 by preventing the formation of structure 3 observed in A beta 40 but not A beta 42, thereby reducing the structural differences between [G22]A beta 40 and [G22]A beta 42 at the N-terminus. [G22]A beta 40 is characterized by a significantly increased amount of average beta-strand relative to the other three peptides due to an induced beta-hairpin structure at R5-H13, similar to structure 2. Consequently, the N-terminal folded structure of the Arctic mutants closely resembles the N-terminal structure of A beta 42, suggesting that both Arctic A beta peptides might assemble into structures similar to toxic A beta 42 oligomers.