In silico Prediction of Two New Conformations of Aβ42 Peptide and Possible Mechanism of Their Aggregation

Abstract

Alzheimer’s disease is one of the most studied neurodegenerative diseases. The cause for most cases of this disease is unknown. However, there are many hypotheses regarding the progression of this disease. One of the hypotheses is the amyloid hypothesis. Amyloid precursor protein present on chromosome 21 is cleaved by β and γ sectretases. The cleaved fragments of this protein, nearly 36–43 residues long aggregates and are deposited as plaque in the brain. These peptides are called amyloid beta (Aβ). One of the peptide is 42 residues long and is well studied. For long, researchers have been trying to understand the factor that triggers this aggregation as well as the structure of 42 residue long amyloid beta (Aβ42). Various reports suggest that Aβ42 can adopt different conformations such as S-shaped and U-shaped beta sheet structure. In this report, we have predicted an L-shaped alpha-helical structure of Aβ42 as well as a beta-turn-beta structure. We have also predicted that aggregation is sequential and monomers are added one after another. Structurally, these aggregates are highly ordered structures which are stable in aqueous environment as compared to the monomers. Thus, hydrophobic forces may be a factor for the aggregation of amyloid beta peptides.

Keywords: Amyloid beta, L-shaped alpha-helix, beta-turn-beta, docking, molecular dynamics simulation

Cite this Article

Arpita Devi. In silico Prediction of Two New Conformations of Aβ42 Peptide and Possible Mechanism of their Aggregation. Research & Reviews: Journal of Computational Biology 2019; 8(1): 1-7p