|3. Inhibition of Protein Aggregation and Protein Stabilization||
Protein aggregation plays an important role in the pathogenesis of many human diseases, such as Alzheimer's and Parkinson's diseases. In these so-called protein conformational diseases, native proteins usually transform into ¦Â-sheet structures and form ordered aggregates (oligomers or fibrils). Therefore, preventing the conformational transition or the assembly of proteins into toxic oligomers or fibrils is the primary goal of many therapeutic strategies. It has been found experimentally that many organic compounds can prevent or reduce the aggregation of proteins into oligomers s or fibrils, but the molecular mechanisms of their effects are still not well understood. We have carried out MD simulations to investigate the molecular mechanisms for the misfolding and aggregation of amyloid-¦Â peptide inhibited by the organic compounds. The thermodynamic interactions between some of the agents and amyloid-¦Â peptide are experimentally analyzed by isothermal titration calorimetry spectroscopic methods. The knowledge received from the computational and experimental studies is expected to help design more effective agents for the inhibition of amyloid-¦Â oligomeric or fibrillar aggregation. Moreover, the molecular mechanisms of the protein stabilization effects of some osmolytes are being studied by MD simulations.