title: Structural analysis of oligomeric and protofibrillar Aβ amyloid pair structures considering F20L mutation effects using molecular dynamics simulations.
abstract: Aβ 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, Aβ amyloid protein disrupts the normal cell function. Because of these concerns, understanding the structural feature of Aβ amyloid protein in detail is crucial. There have been some efforts on lowering the structural stabilities of Aβ amyloid fibrils by decreasing the aromatic residues characteristic and hydrophobic effect. Yet, there is a lack of understanding of Aβ amyloid pair structures considering those effects. In this study, we provide the structural characteristics of wildtype (WT) and phenylalanine residue mutation to leucine (F20L) Aβ amyloid pair structures using molecular dynamics simulation in detail. We also considered the polymorphic feature of F20L and WT Aβ pair amyloids based on the facing β-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 Aβ 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. Proteins 2017; 85:580-592. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Myeongsang
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Inchul
authors.initials: I
authors.lastname: Baek
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Sungsoo
authors.initials: S
authors.lastname: Na
mesh_terms: D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D007930:Leucine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D011485:Protein Binding; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D055550:Protein Stability; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C086839:amyloid beta-protein (17-42); D010649:Phenylalanine; D007930:Leucine
keywords: F20L Aβ amyloid pair; aromatic residue effect; leucine residue mutation; polymorphic structures; size effect; structural stability