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