Amyloid Fibril Design: Limiting Structural Polymorphism in Alzheimer's Aβ Protofilaments.

ABSTRACT: Nanoscale fibrils formed by amyloid peptides have a polymorphic character, adopting several types of molecular structures in similar growth conditions. As shown by experimental (e.g., solid-state NMR) and computational studies, amyloid fibril polymorphism hinders both the structural characterization of Alzheimer's Aβ amyloid protofilaments and fibrils at a molecular level, as well as the possible applications (e.g., development of drugs or biomarkers) that rely on similar, controlled molecular arrangements of the Aβ peptides in amyloid fibril structures. We have explored the use of several contact potentials for the efficient identification of minimal sequence mutations that could enhance the stability of specific fibril structures while simultaneously destabilizing competing topologies, c

SUBMITTER: Tywoniuk B 

PROVIDER: S-EPMC6472267 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature