Computational design of new Peptide inhibitors for amyloid Beta (aβ) aggregation in Alzheimer's disease: application of a novel methodology.

ABSTRACT: Alzheimer's disease is the most common form of dementia. It is a neurodegenerative and incurable disease that is associated with the tight packing of amyloid fibrils. This packing is facilitated by the compatibility of the ridges and grooves on the amyloid surface. The GxMxG motif is the major factor creating the compatibility between two amyloid surfaces, making it an important target for the design of amyloid aggregation inhibitors. In this study, a peptide, experimentally proven to bind Aβ40 fibrils at the GxMxG motif, was mutated by a novel methodology that systematically replaces amino acids with residues that share similar chemical characteristics and subsequently assesses the energetic favorability of these mutations by docking. Successive mutations are combined and reassessed via d

SUBMITTER: Eskici G 

PROVIDER: S-EPMC3675214 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature