Conformational changes of Aβ (1–42) monomers in different solvents

Abstract

Amyloid proteins are known to be the main cause of numerous degenerative and neurodegenerative diseases. In general, amyloids are misfolded from monomers and they tend to have β-strand formations. These misfolded monomers are then transformed into oligomers, fibrils, and plaques. It is important to understand the forming mechanism of amyloids in order to prevent degenerative diseases to occur. Aβ protein is a highly noticeable protein which causes Alzheimer’s disease. It is reported that solvents affect the forming mechanism of Aβ amyloids. In this research, Aβ1–42 was analyzed using an all-atom MD simulation with the consideration of effects induced by two disparate solvents: water and DMSO. As a result, two different conformation changes of Aβ1–42 were exhibited in each solvent. It was found that salt-bridge of Asp23 and Lys28 in Aβ1–42 was the key for amyloid folding based on the various analysis including hydrogen bond, electrostatic interaction energy and salt-bridge distance. Since this salt-bridge region plays a crucial role in initiating the misfolding of Aβ1–42, this research may shed a light for studies related in amyloid folding and misfolding.