title: Structural and Material Properties of Amyloid Aβ40/42 Fibrils.
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.
authors.affiliation: School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Chemistry, University of Miami, Coral Gables, Florida, 33146, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Paul
authors.affiliation: Department of Chemistry, University of Miami, Coral Gables, Florida, 33146, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Hoffmann
authors.affiliation: Department of Natural Science, Albany State University, Albany, GA, 31705, USA.
authors.forename: Kwaichow
authors.initials: K
authors.lastname: Chan
authors.affiliation: School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China.
authors.forename: Dingkun
authors.initials: D
authors.lastname: Hu
authors.affiliation: School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China. chm_aihq@ujn.edu.cn.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Ai
authors.affiliation: Department of Chemistry, University of Miami, Coral Gables, Florida, 33146, USA. rpr@miami.edu.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Prabhakar
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C538897:amyloid beta-protein (40-42)
keywords: conformation analysis; helical structures; materials science; mechanical properties; molecular dynamics