Structural analysis of the Aβ(15-40) amyloid fibril based on hydrophobicity distribution

• DOI: 10.18388/abp.2018_2647
• Publication Date: 2018-11-21T13:37:40Z
• Authors: Dawid Dułak; Mateusz Banach; Malgorzata Gadzała; Leszek Konieczny; Irena Roterman
• Keywords: 0301 basic medicine; Protein Folding; 03 medical and health sciences; Amyloid beta-Peptides; Models, Chemical; Mutation; Humans; Computer Simulation; Neurodegenerative Diseases; Hydrophobic and Hydrophilic Interactions; Peptide Fragments

The Aβ42 amyloid is the causative factor behind various neurodegenerative processes. It forms elongated fibrils which cause structural devastation in brain tissue. The structure of an amyloid seems to be a contradiction of protein folding principles. Our work focuses on the Aβ(15-40) amyloid containing the D23N mutation (also known as the “Iowa mutation”), upon which an in silico experiment is based. Models generated using I-Tasser software as well as the fuzzy oil drop model – regarded as alternatives to the amyloid conformation – are compared in terms of their respective distributions of hydrophobicity (i.e. the existence of a hydrophobic core). In this process, fuzzy oil drop model parameters are applied in assessing the propensity of selected fragments for undergoing amyloid transformation.