MMPBSA Decomposition of the Binding Energy throughout a Molecular Dynamics Simulation of Amyloid-Beta (Aß10−35) Aggregation

Abstract

Recent experiments with amyloid-beta (Aβ) peptides indicate that the formation of toxic oligomers may be an important contribution to the onset of Alzheimer’s disease. The toxicity of Aβ oligomers depend on their structure, which is governed by assembly dynamics. However, a detailed knowledge of the structure of at the atomic level has not been achieved yet due to limitations of current experimental techniques. In this study, replica exchange molecular dynamics simulations are used to identify the expected diversity of dimer conformations of Aβ10−35 monomers. The most representative dimer conformation has been used to track the dimer formation process between both monomers. The process has been characterized by means of the evolution of the decomposition of the binding free energy, which provides an energetic profile of the interaction. Dimers undergo a process of reorganization driven basically by inter-chain hydrophobic and hydrophilic interactions and also solvation/desolvation processes.

Keywords

• Alzheimer’s disease
• amyloid-beta (Aβ) peptides
• dimerization
• replica exchange molecular dynamics (REMD)
• binding free energy calculations
• Kepler scientific workflow