Document Type : Research Paper

Authors

• Kaveh Khodayari ¹
• Parviz Abdolmaleki ²

¹ Biophysics, Biological Sciences, Tarbiat Modares, Tehran, Iran

² Biophysics, Faculty of Biological Sciences, Tarbiat Modares University,Tehran,Iran

Abstract

Aggregation of proteins lead to form amyloid diseases including Alzheimer's disease, Parkinson and diabetes type II has been increasingly understudying recently. Compounds including indole rings are the best amyloid aggregation inhibitors. Experimental studies have shown that bis( indolyl )-2-methyl phenyl methane (BI2MPM) has a great inhibitory potential on Lysozyme amyloid fibril formation, While bis( indolyl )-3-nitrophenyl methane (BI3NPM) showed weak 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 for both ligands to amyloid nucleus model but different binding positions. Molecular dynamics simulation showed that BI2MPM apply major degradation on the beta structure of early fibril precursors, leading 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.

Keywords

• Amyloid Diseases
• Beta structure
• Indole Ring
• Molecular Dynamics
• Pi interactions