Computational molecular modeling for the assessment of nanoparticle toxicity: interactions with biomolecules.
Yanamala-N; Kagan-VE; Shvedova-AA
Toxicologist 2014 Mar; 138(1):607
Over the past two decades, nanotechnology has emerged as a key player in various disciplines of science and technology. A detailed understanding of the molecular details of interactions between nanoparticles (NP) and biomolecules is crucial for obtaining adequate information on mechanisms of action of nanomaterials and their possible toxicological outcomes. There has been a recent surge in the application of in silico based methods and approaches to address interactions of NPs with biomolecules providing insights into their mechanisms. To do this, we used structure- based computational modeling as a tool to predict the molecular interactions between carbonaceous NPs and cellular proteins and lipids. We demonstrated that specific interactions of NPs with proteins/lipids resulted in a coating on its surface, ultimately masking their inherent properties, thus leading to modified distribution in cells, recognition and uptake by cells. We also provide evidence that interactions of basic/positively charged amino acids of the enzymes (e.g. peroxidases) with the carboxyl moieties on carbon nanotubes and graphene - positioning them in close proximity to the catalytic site of the enzyme - are essential for the effective catalysis and safe degradation of these materials in vivo. Structure based computational modeling is a useful and effective approach that could facilitate the design and development of safe engineered nanomaterials.
Toxicology; Nanotechnology; Molecular-biology; Molecular-structure; Models; Cell-function; Cellular-function; Lipids; Proteins; Amino-acids; Enzymes
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona