Inhibitory mechanism of n-MTAB AuNPs for alpha-synuclein aggregation

Objective The aggregation of alpha-synuclein (alpha-syn) is closely related to the pathogenesis and dysfunction of Parkinson's disease. Methods To investigate the potential of nanoparticlemediated therapy, the interactive mechanism between alpha-syn and n-myristyltrimethylammonium bromide (MTAB) Gold nanoparticles (AuNPs) with different diameters was explored by molecular dynamics simulations. Results The results indicated that there was a directional interaction between alpha-syn and n-MTAB AuNPs, in which the driving force for the binding of the C-ter minus in alpha-syn came from electrostatic interactions and the nonamyloid beta component (NAC) domain exhibited weak hydrophobic interactions as well as electrostatic interaction, thereby preventing alpha-syn aggregation. Energy statistics and analysis showed that for 5-MTAB AuNPs, acidic amino acids such as Glu and Asp played a very important role. Conclusions This study not only demonstrated a theoretical foundation for the behavior of biomolecules directionally adsorbed on the surface of biofunctional nanoparticles but also indicated that 5-MTAB AuNPs may be a potential inhibitor against alpha-syn protein aggregation.