Strategies for Molecular Simulations in Studying Aβ Aggregation and Aβ Aggregation Inhibitors for Alzheimer’s Disease Therapy
Posted: 10 Feb 2020
Date Written: January 18, 2020
One of the important pathological factors in the treatment of Alzheimer’s disease (AD) is aggregation of beta-amyloid (Aβ) peptides. Proteolytic cleavage, destabilization, reversal or inhibition of aggregation of these Aβ peptides forms the basis for different disease modifying strategies in the treatment of AD. New strategies are being developed that focus on alleviating the problems associated with this Aβ aggregation using computational approaches namely molecular dynamic (MD) simulations. Particular emphasis in MD simulations is on the oligomerization of Aβ monomers via toxic intermediate forms into fibrils that are the characteristic depositions seen in AD afflicted brains. This helps in understanding the mechanism of aggregation and could help in the further development of therapeutic or diagnostic molecules against AD. Further computational strategy utilized is to use structure-based drug design (SBDD) by docking to understand the interactions between the therapeutic or diagnostic agents and the different Aβ forms. Such studies of the Aβ-Aβ or Aβ-drug interactions help in comprehending and altering the course of aggregation of the Aβ peptides and might help in designing molecules for therapy or diagnosis of AD. Thus MD simulations seem to play an important role in not only understanding the molecular level processes of aggregation and binding but also in the potential drug design of therapeutics and possibly diagnostics for AD.
This poster will deal with the different molecular simulation strategies for studying Aβ aggregation and Aβ aggregation inhibitors.
Keywords: Alzheimer's disease, molecular dynamics, molecular simulations, Aβ aggregation, Aβ aggregation inhibitors, structure based drug design
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