Structural and Material Properties of Amyloid A[beta]40/42 Fibrils

• Published in: Chemphyschem Vol. 17; no. 16; p. 2558
• Main Authors: Dong, Mingyan, Paul, Thomas J, Hoffmann, Zachary, Chan, Kwaichow, Hu, Dingkun, Ai, Hongqi, Prabhakar, Rajeev
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 18.08.2016
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.201600256

In this study, structural and mechanical properties of a series of models of A[beta]42 (one- and two-fold) and A[beta]40 (two- and three-fold) fibrils have been computed by using all-atom molecular dynamics simulations. Based on calculations of the twist angle ([theta]) and periodicity (v=360d/[theta]), oligomers formed by 20, 11, and 13 monomers were found to be the smallest realistic models of three-fold A[beta]40, one-fold A[beta]42, and two-fold A[beta]42 fibrils, respectively. Our results predict that the A[beta]40 fibrils initially exist in two staggered conformations [STAG(+2) and STAG(+1)] and then undergo a [STAG(+2)[arrow right]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 A[beta]40 and A[beta]42 fibrils. A comparison of the computed potential energy suggests that a two-fold A[beta]40 aggregate is more stable than its three-fold counterpart, and that A[beta]42 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 50GPa and 0.95GPa, respectively, show that these aggregates possess excellent material properties.