Conformational Features of Aβ25-35 and Its Mutants Suggest Toxic Structural Determinants: Insights from REST2 Simulations.

Abstract excerpt

The Aβ25-35 fragment is the shortest proteolytic fragment retaining the core neurotoxicity of full-length Alzheimer's amyloid-β (Aβ). To elucidate the structure-neurotoxicity relationships, we performed replica exchange with solute tempering 2 (REST2) simulations on wild-type (WT), N27A (less toxic), and M35A (more toxic) Aβ25-35 hexamers in explicit solvent. Our simulations show that N27A, WT, and M35A hexamers...

Topics

• Amyloid beta-Peptides
• Peptide Fragments
• Molecular Dynamics Simulation
• Mutation
• Hydrophobic and Hydrophilic Interactions