Understanding the Interaction Between Nanoscale Building Blocks and Biologically Relevant Molecules
X. Zhao (CNMS Postdoc), A. Striolo (U of Oklahoma, now CNMS User), and P. T. Cummings (CNMS Staff)
Scientists at Oak Ridge National Laboratory’s new Center for Nanophase Materials Sciences (CNMS) are leading the way in developing detailed molecular-level understanding of how nanomaterials may interact with biologically important molecules. A provocative experimental study, published in 2004, suggested that juvenile largemouth bass, when exposed to plain fullerenes (C60 “buckyballs”) suspended in water, exhibited oxidative stress, indicating that the fullerenes can be absorbed into living tissue. This led CNMS researchers to investigate the potential impact of buckyballs if they managed to penetrate not only into cells but into the cell nucleus to interact with DNA. With the molecular simulation tools and computing hardware available today, it is possible to ask this question computationally before carrying out experiments. The surprising prediction  is that buckyballs bind very strongly to DNA, with binding energies of between -27 and -42 kcal/mol (i.e., about 50 to 80 times larger than typical kinetic energies at room temperature). The binding is so strong that it deforms the DNA; it appears to impact the ability of DNA to self-repair; and it is likely to interfere with replication, resulting in significant health risks, if we presume that there is a way for buckyballs to reach the cell nucleus. However, these findings need to be confirmed experimentally.
Neutron scattering experiments now are planned in collaboration with researchers in the Spallation Neutron Source at ORNL to verify the predicted deformation of DNA. Additionally, the likelihood of buckyballs penetrating cell membranes and the cell nucleus must be determined by a combination of experimental and computational techniques.
Using the computational expertise and tools at the CNMS and ORNL for early evaluation of potential nanotoxicological risk is a prudent and economical way to identify and understand potential risks before nanomaterials are used (or are even available) on a large scale.
Long (up to 20 ns in length) molecular dynamics simulations of DNA strands in aqueous solution with C60 fullerenes exhibit strong binding to both the end (above right) and minor groove (below right) of double strand DNA. Similar results are obtained for single strand DNA.