Poster Presentation Melbourne Protein Group Student Symposium 2013

Dimensionality of carbon nanomaterials determines the aggregation propensity of amyloidogenic peptides: multiscale theoretical simulations  (#50)

Adam J Makarucha 1 , Nevena Todorova 1 , Irene Yarovsky 1 , Arash Mostofi 2 , Nicholas D M Hine 2
  1. RMIT, Melbourne, Vic, Australia
  2. Imperial College, London

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of so-called protein aggregation diseases such as Alzheimer’s, Parkinson’s and prion disease caused by aggregation and fibril formation of amyloid-prone proteins1. Computational studies have been employed to investigate the effects of nanomaterials on many of these biological systems due to their ability to reach spatial and temporal resolutions that are unattainable by modern experimental techniques2

We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the extended contact area available for π-stacking between the aromatic residues of the peptide and the flat surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide such as that observed in the presence of C60 can be unfavorable for like-peptide interactions and the formation of fibril competent structures. In contrast, the extended peptide conformations promoted by the nanotube and graphene surfaces can induce peptide self-assembly and provide a template for fibril-growth.