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-beta (A beta) 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 A beta(13-23) (the core recognition site of A beta) and full-length A beta(1-42). Umbrella sampling MD calculations have been used to estimate the free energy of binding, Delta G, of these peptides to A beta(13-23). The highest Delta G(binding) is found for SGB1. Each of the pseudo-peptides was also docked to A beta(1-42) and subjected up to seven microseconds of all atom molecular dynamics simulations. The resulting structures lend insight into how the dynamics of A beta(1-42) 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.