We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Molecular dynamics studies of a β-sheet blocking peptide with the full-length amyloid beta peptide of Alzheimer's disease.
- Authors
Amini, Zohreh; Fatemi, Mohammad Hossein; Rauk, Arvi
- Abstract
The region encompassing residues 13-23 of the amyloid beta peptide (Aβ(13-23)) of Alzheimer's disease is the self-recognition site that initiates toxic oligomerization and fibrillization. A number of pseudopeptides have been designed to bind to Aβ(13-23) and been computationally shown to do so with high affinity. More interactions are available in full-length Aβ than are available in the shorter peptide. We describe herein a study by molecular dynamics (MD) of nine distinct complexes formed by one such pseudopeptide, SGA1, with full-length beta amyloid, Aβ(1-42). The relative stabilities of the Aβ-SGA1 complexes were estimated by a combination of MD and ab initio methods. The most stable complex, designated AB1, was found to be one in which SGA1 is bound to the self-recognition site of Aβ(1-42) in an antiparallel β-sheet fashion. Another complex, designated AB3, also involved SGA1 binding to the self-recognition region of Aβ(1-42), albeit with lower affinity. In both AB1 and AB3, SGA1 formed antiparallel β-sheets but to opposite edges of Aβ. A complex, AB4, with similar stability to AB3, was found with a parallel β-sheet in the self-recognition site. A fourth complex, AB7, also with similar stability, formed a parallel β-sheet in the hydrophobic central region of Aβ. In all cases, complexation of SGA1 induced extensive β-sheet structure in Aβ(1-42).
- Subjects
AMYLOID beta-protein; ALZHEIMER'S disease; OLIGOMERIZATION; MOLECULAR dynamics; MOLECULAR physics
- Publication
Canadian Journal of Chemistry, 2016, Vol 94, Issue 10, p833
- ISSN
0008-4042
- Publication type
Article
- DOI
10.1139/cjc-2016-0267