Computational simulations to decipher drug properties
2017
Sharif University of Technology, Tehran, Iran
Aggregation of amyloid-beta is one of the main hallmarks of Alzheimer's disease. Different strategies are being investigated to inhibit its polymerization and/or avoid amyloid formation. Here, molecular dynamics is used to elucidate the interactions of RS-0406 with different amyloid-beta polymers. RS-0406, a small organic molecule, has already shown promising results in inhibiting amyloid formation in vitro. Using experimental and computational log P values, the researchers are able to describe different mechanisms by which RS-0406 affects the conformational stability of the polymers. They found that it affects both the stabilization of monomers and the destabilization of fibril structures. In summary, with this method, it is possible to describe the unique structural features from this small molecule that affect the amyloid formation and the mechanisms behind its effect. This platform could be used to investigate drug-related properties and drug interactions with protein structures to better understand their mechanisms and design better therapeutic strategies.
Inhibition mechanisms of a pyridazine-based amyloid inhibitor: as a β-sheet destabilizer and a helix bridge maker
Hamid R Kalhor
Added on: 08-10-2021
[1] https://pubs.acs.org/doi/10.1021/acs.jpcb.7b05189[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
