Computational Modeling Investigating the Interactions of Proteins with Fullerene-based Nanoparticles

Aalto University, P.O. Box 11000, FI-00076 Aalto www.aalto.fi Author Praveen Nedumpully Govindan Name of the doctoral dissertation Computational Modeling Investigating the Interactions of Proteins with Fullerene-based Nanoparticles Publisher School of Science Unit Department of Applied Physics Series Aalto University publication series DOCTORAL DISSERTATIONS 12/2013 Field of research Engineering Physics, Theoretical and Computational Physics Manuscript submitted 28 September 2012 Date of the defence 15 January 2013 Permission to publish granted (date) 21 December 2012 Language English Monograph Article dissertation (summary + original articles) Abstract In this work, the effects of fullerene-based nanoparticles (fullerene and two of its derivatives) on the structure and functioning of proteins were investigated. An approach combining two computational methods — molecular docking and molecular dynamics simulations — was used. The studies were based on, and complement experiments on the effects on nanoparticles on proteins.In this work, the effects of fullerene-based nanoparticles (fullerene and two of its derivatives) on the structure and functioning of proteins were investigated. An approach combining two computational methods — molecular docking and molecular dynamics simulations — was used. The studies were based on, and complement experiments on the effects on nanoparticles on proteins. To make a better prospective, first, the properties of nanoparticle clusters in water were studied. The nature and stability of the clusters were found to depend on the surface properties of the nanoparticle. Nanoparticles with hydrophobic surfaces made strong and stable clusters, whereas hydrophilic nanoparticles made loose associations whose structure changed over time. In addition, the effects of nanoparticles on the secondary structure of small peptides were studied. For some peptides, a small increase in the alpha-helix content was observed in the presence of nanoparticles. For protein-nanoparticle interactions, the inhibition of an enzyme protein, namely taq DNA polymerase, by fullerene derivatives was studied. Based on our studies, we predicted that the inhibition was caused by tertiary structural changes of the protein induced by the nanoparticles. Point mutation studies which could be used to examine our predictions were also proposed. In another study, the inhibition of tubulin self-assembly into microtubules by fullerene species was investigated. Simulation studies indicated that binding of nanoparticles to certain locations on tubulin was responsible for the inhibition. These binding sites are important for self-assembly as they are located in areas that make contact with the neighboring tubulins in microtubules. Finally, interactions of FUL and FUOH nanoparticles with ubiquitin was studied. Two more prominent binding sites, including one near the C-terminal tail was observed, and the biological implications of the binding are discussed.