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

ABSTRACT: A causative factor for neurotoxicity associated with Alzheimer's disease is the aggregation of the amyloid-? (A?) 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?_13?23 (the core recognition site of A?) and full-length A?_1?42. Umbrella sampling MD calculations have been used to estimate the free energy of binding, ?G, of these peptides to A?_13?23. The highest ?G_binding is found for SGB1. Each of the pseudo-peptides was also docked to A?_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?_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.

SUBMITTER: Mehrazma B 

PROVIDER: S-EPMC6225248 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature