d-Amino Acid Pseudopeptides as Potential Amyloid-Beta Aggregation Inhibitors.

A causative factor for neurotoxicity associated with Alzheimer's disease is the aggregation of the amyloid-β (Aβ) peptide into soluble oligomers. Two all d-amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation. Molecular dynamics (MD) simulations have been carried out to study the interaction of the pseudo-peptides with both Aβ (the core recognition site of Aβ) and full-length Aβ. Umbrella sampling MD calculations have been used to estimate the free energy of binding, ∆G, of these peptides to Aβ. The highest ∆G is found for SGB1. Each of the pseudo-peptides was also docked to Aβ and subjected up to seven microseconds of all atom molecular dynamics simulations. The resulting structures lend insight into how the dynamics of Aβ are altered by complexation with the pseudo-peptides and confirmed that SGB1 may be a better candidate for developing into a drug to prevent Alzheimer's disease.