Effect of fullerenol surface chemistry on nanoparticle binding-induced protein misfolding

Research output: Contribution to journalArticle

Researchers

  • Slaven Radic
  • Praveen Nedumpully-Govindan
  • Ran Chen
  • Emppu Salonen

  • Jared M. Brown
  • Pu Chun Ke
  • Feng Ding

Research units

  • Clemson University
  • University of Colorado Anschutz Medical Campus

Abstract

Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation - a common strategy for solubilizing and functionalizing fullerene - on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We found that all derivatives bound to the model protein. Specifically, the more hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the surface of the protein via hydrogen bonds, which stabilized the protein without inducing large conformational changes in the protein structure. In contrast, fullerene derivatives with a smaller number of hydroxyl groups buried their hydrophobic surface inside the protein, thereby causing protein denaturation. Overall, our results revealed a distinct role of surface chemistry on nanoparticle-protein binding and binding-induced protein misfolding.

Details

Original languageEnglish
Pages (from-to)8340-8349
Number of pages10
JournalNanoscale
Volume6
Issue number14
Publication statusPublished - 21 Jul 2014
MoE publication typeA1 Journal article-refereed

ID: 9327658