Prediction of the Bio-Physical Chrateristics of Beta-Amyloid Mixture Based on Amino Acid Sequence

Abstract

Amyloid beta (Aβ) is the ∼4-k Da peptide originated from amyloid precursor protein (APP) by three different type of the secretases (α , β ,λ). Among them, two β and λ secretases are known to involve the production of the 40 residues (Aβ 40) and 42 residues (Aβ42). Aβ 40 and Aβ42 are main constituent of plaques found in Alzheimer's disease (AD). The shorted one Aβ 40 is found mainly in cerebrovascular amyloid. Aβ42 is the major components in amyloid plaques core deposits and more neuro toxicity. The first 16 residues of Aβ 40 and Aβ42 are largely hydrophobic and the rest of them are very hydrophobic. The most abundant Aβ 40 and Aβ42 in a ratio are about 10:1. Although there are the small differences between two peptides, they show the significantly different biochemical characteristics. A lot of studies have suggested that the soluble oligomeric intermediates are more prone to be a cause of AD than insoluble fibrils including spherical particles and curvilinear structures called “protofibrils” . In addition to these interesting chemical characteristics and pathogenecity of Aβ, the relationship between the structure and composition ratio of Aβ and the occurrence of AD is also intensively studied. However, most of them are mainly focused on the one type of Aβ such as Aβ 40 or Aβ42. In this study, we predicted the basic characteristic of Aβ mixture employing the computational chemistry and binding affinities of the small organic molecules including the very short peptides. The results from the calculation indicated that the change of the composition ratio of the Aβ caused the significant change at the characteristics and binding affinities.