ABSTRACT
An important feature of Alzheimer’s disease is that the toxic species of the amyloid-ß protein (Aß) might be both soluble oligomers and insoluble fibrils. This finding makes Aß oligomers attractive therapeutic targets. A detailed experimental characterization of the Aß oligomeric intermediates is thus far very difficult and only limited data are available because the intermediates are typically short-lived and are present in a wide range of conformations and degrees of aggregation. Activation Relaxation technique (ART) can be used to optimize any cost function in a high-dimensional space through a series of activated steps. Analysis of the lowest-energy structures generated by all ART simulations shows several interesting features. The OPEP potential form was optimized on the structures of six monomeric peptides with 10-38 residues adopting various secondary structures in solution.
