Design of heparin oligosaccharide based molecules for inhibition of Alzheimer amyloid beta (Aβ40) aggregation

In this computational study, we have combined molecular docking and molecular dynamics (MD) simulation techniques to explore interactions of monomeric and aggregated forms of Alzheimer's amyloid beta (A beta(40)) with seven chemically distinct heparin derived glycoaminoglycans (GAGs) referred to as ADC, SDC, DC, V1, V2, V3, and V4. The docking procedure proposed two major binding sites, i.e., one present at the top of the fibril (site A), and the other located in the hairpin region (site B). Due to its position, site B offers an interesting target to design molecules with anti-aggregation properties. Our results predicted that out of seven GAGs, only three of them (ADC, SDC, and DC) bind to site B. The identification of these molecules can advance our efforts to develop therapeutic interventions for this deadly disease.