Deciphering molecular mechanism of amyloid inhibition through docking studies between amyloid beta peptide and selected small molecules

Abstract

The misfolding and aggregation of proteins into amyloids has been linked to a large group of variety amyloid -related diseases. This group consists of variety human diseases such as Alzheimers disease, Parkinson’s disease, Hungtington’s disease, atherosclerosis etc. Aggregation of proteins, such as aâ in Alzheimer’s disease, appears to lead to the formation of toxic assemblies. These assemblies can be very small in size like oligomers(consisting of very few proteins) and can reach a maximum of thousands of proteins which leads to fibril formation. It has been found out that inhibiting the aggregation of these proteins could slow down the process of formation of these neurodegerative diseases. But still there is truancy of a possible therapy that could effectively prevent the formation of amyloid fibrils. Thus in present study we try to understand the mechanism by which the small compounds which we have selected inhibits the target protein or the amyloid beta peptide. Here we understand the type of interaction and whether the compounds binds near the amyloidogenic region. We have also tried to understand the binding between two amyloid protein. Here we have choosen an amyloidogenic protein beta amyloid (1-42), pdbid-1IYT, that is processed from the amyloid precursor protein(APP). While best known as the component of amyloid plaques in association with Alzheimer’s disease, as A-beta is the main component of certain deposits found in the brain of patients with Alzheimer’s disease. The small compounds selected here are mostly cholesterol reducing agents such as statins, wine related compounds, green tea related components, polyphenols, phenothiazines. These compounds are found to inhibit amyloid fibrillogenesis in vivo. So here we adduce a mechanism by which these small compounds inhibit the aggregation of amyloid beta(1-42)peptide.