Molecular simulation to aid in the understanding of the A beta(1-42) peptide of Alzheimer's disease

The A beta (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 A beta peptide. This part is an apolar a-helix. The remaining residues form beta -sheets. Aggregation requires that beta -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 A beta peptides, blocking so the associations between the beta -strains.