Influence of EGCG on α‐synuclein (αS) aggregation and identification of their possible binding mode: A computational study using molecular dynamics simulation

The accumulation of intrinsically disordered α‐synuclein (αS) protein that can form β‐sheet‐rich fibrils is linked to Parkinson's disease. (−)‐Epigallocatechin‐3‐gallate ( EGCG ) is the most abundant active component in green tea and can inhibit the fibrillation of αS. The elucidation of this molecular mechanism will be helpful to understand the inhibition mechanism of EGCG to the fibrillation of αS and also to find more potential small molecules that can inhibit the aggregation of αS. In this work, to study the influence of EGCG on the structure of β‐sheet‐rich fibrils of αS and identification of their possible binding mode, molecular dynamics simulations of pentamer and decamer aggregates of αS in complex with EGCG were performed. The obtained results indicate that EGCG can remodel the αS fibrils and break the initial ordered pattern by reducing the β‐sheet content. EGCG can also break the Greek conformation of αS by the disappeared H‐bond in the secondary structure of turn. The results from our study can not only reveal the specific interaction between EGCG and β‐sheet‐rich fibrils of αS, but also provide the useful guidance for the discovery of other potential inhibitors.