Amyloid-beta oligomerization dynamics
October 2017
University of California, Davis, USA
The amyloid-beta peptide in its oligomeric form is a major pathogenic element in the development of Alzheimer's disease. In this study, the researchers aim to quantify the binding of pyrroline-nitroxyl fluorene, an amyloid-beta toxicity blocker, and its effect on the peptide. The results show that the binding affinity depends on the oligomeric state of amyloid-beta, being easier to be bound when it is in its monomer or dimer form compared to its oligomeric forms. To further understand the dynamics of these interactions, a molecular dynamics simulation is used together with molecular docking to define conformational states that correlate to lower toxicity and aggregation propensity of amyloid-beta. This study brings new mechanistic insights of pharmaceutical relevance and develops a methodology to increase the "in vivo" relevance of the results, providing a platform to investigate the potential modulation of peptide aggregation as a therapeutic target in other disorders.
Oligomerization alters binding affinity between amyloid beta and a modulator of peptide aggregation
John C Voss
Added on: 08-10-2021
[1] https://pubs.acs.org/doi/10.1021/acs.jpcc.7b06164[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
