Theoretical Analysis of the Aggregation-Inhibition Effect of Arginine on Polyglutamine Protein by the Generalized-Ensemble Method

Abstract

The aggregation of polyglutamine (polyQ) proteins, which have the abnormal expansion of glutamine repeats, is a critical pathological hallmark of polyQ diseases. Experimental studies have shown an amino acid arginine uniquely inhibits the polyQ-protein aggregation. We performed replica-permutation molecular dynamics simulations to clarify the inhibitory effects of arginine on the polyQ-protein aggregation. We found arginine makes more contact with the polyQ protein than lysine, and this tendency of arginine likely inhibits the polyQ-protein aggregation.