Molecular Simulation to Aid in the Understanding of the Aβ(1–42) Peptide of Alzheimer's Disease

Abstract

The Aβ(1–42) peptide of Alzheimer's disease was studied by molecular modeling. The coordinates of the peptide were experimentally generated from solution-NMR spectroscopy, and the conformations were energy minimized using a combination of connectivity-based iterative partial equalization of orbital electronegativity with the MM + force field.

There is a central folded domain in the Aβ peptide. This part is an apolar α-helix. The remaining residues form β-sheets. Aggregation requires that β-sheets interact by noncovalent bonding forces. The unsoluble, aggregated complexes are energetically stable and have ordered structures.

A perspective in drug research is to design compounds that inhibit the hydrophobic cores of the individual Aβ peptides, blocking so the associations between the β-strains.

Key Words:

• Molecular simulation
• Morbus Alzheimer
• Amyloid
• Aggregation of peptides
• Aβ peptides
• a-helix
• β-sheet
• Conformational transitions
• Hydrophobic cores of β-sheets
• Drug design