Abstract
In this study, structural and mechanical properties of a series of models of Aβ42 (one‐ and two‐fold) and Aβ40 (two‐ and three‐fold) fibrils have been computed by using all‐atom molecular dynamics simulations. Based on calculations of the twist angle (θ) and periodicity (v=360d/θ), oligomers formed by 20, 11, and 13 monomers were found to be the smallest realistic models of three‐fold Aβ40, one‐fold Aβ42, and two‐fold Aβ42 fibrils, respectively. Our results predict that the Aβ40 fibrils initially exist in two staggered conformations [STAG(+2) and STAG(+1)] and then undergo a [STAG(+2)→STAG(+1)] transformation in a size‐dependent manner. The length of the loop region consisting of the residues 23–29 shrinks with the elongation of both Aβ40 and Aβ42 fibrils. A comparison of the computed potential energy suggests that a two‐fold Aβ40 aggregate is more stable than its three‐fold counterpart, and that Aβ42 oligomers can exist only in one‐fold conformation for aggregates of more than 11 monomers in length. The computed Young′s modulus and yield strengths of 50 GPa and 0.95 GPa, respectively, show that these aggregates possess excellent material properties.
Predicting properties: Relaxed minimum models to probe the structural and material properties of mature Aβ fibrils with N=11 and 13 for one‐fold and two‐fold Aβ42 morphologies, respectively, and with N=20 for both two‐fold and three‐fold Aβ40 morphologies are predicted.
