Study of Inhibition Potential of Synthetic Bis-Indole Compounds on Amyloid Fibrillation by Molecular Simulation Methods

Aggregation of proteins lead to form amyloid diseases including Alzheimer, Parkinson and diabetes type II has been increasingly considered recently. Compounds including indole rings are the best amyloid aggregation inhibitors. Experimental studies have shown that bis(indolyl)-2-methyl[H1] [M2] phenylmethane (BI2MPM) has a great [H3] [M4] inhibitory potential on Lysozyme amyloid fibril formation, While bis(indolyl)-3-nitrophenylmethane [M5] (BI3NPM) has shown weaker inhibitory power. In this study, the interaction of these two ligands was investigated on amyloid model protein using molecular docking and molecular dynamics simulation techniques. Molecular Docking method showed similar reluctance to both ligands in amyloid nucleus model but in different binding positions. Molecular dynamics simulation showed that BI2MPM with major degradation on the beta structure of early fibril precursors, leads to lower interaction. It also increases structural changes in the subtypes of beta-strands and induces instability and stops fibrillation growth, but BI3NPM has minimum changes on the fibrils core structures.