Structural analysis of oligomeric and protofibrillar A beta amyloid pair structures considering F20L mutation effects using molecular dynamics simulations

Abstract

A beta amyloid proteins are involved in neuro-degenerative diseases such as Alzheimer's, Parkinson's, and so forth. Because of its structurally stable feature under physiological conditions, A beta amyloid protein disrupts the normal cell function. Because of these concerns, understanding the structural feature of A beta amyloid protein in detail is crucial. There have been some efforts on lowering the structural stabilities of A beta amyloid fibrils by decreasing the aromatic residues characteristic and hydrophobic effect. Yet, there is a lack of understanding of A beta amyloid pair structures considering those effects. In this study, we provide the structural characteristics of wildtype (WT) and phenylalanine residue mutation to leucine (F20L) A beta amyloid pair structures using molecular dynamics simulation in detail. We also considered the polymorphic feature of F20L and WT A beta pair amyloids based on the facing beta-strand directions between the amyloid pairs. As a result, we were able to observe the varying effects of mutation, polymorphism, and protofibril lengths on the structural stability of pair amyloids. Furthermore, we have also found that opposite structural stability exists on a certain polymorphic A beta pair amyloids depending on its oligomeric or protofibrillar state, which can be helpful for understanding the amyloid growth mechanism via repetitive fragmentation and elongation mechanism. (C) 2016 Wiley Periodicals, Inc.