Development of a Coarse-Grained Model to Study DNA Interactions with Nanomaterials

Hybrid nanostructures composed of single-walled carbon nanotubes (SWCNT) coated with single stranded DNAs (ssDNA) are of great interest due to their various applications in the nanotechnology and biomedical field. In particular, short oligonucleotides in biofluids can be promising disease biomarkers, while carbon nanotubes prove to be an ideal material for implantable biosensors. Although ssDNA-coated-SWCNT particles have been a focus of recent studies, the mechanism and energetics of DNA-nanotube binding process are not yet fully understood. To address this, we developed a coarse-grained model to study DNA-SWCNT interactions. Adopting an existing 2nd generation of 3-Site-Per-Nucleotide (3SPN.2) coarse-grained DNA model, in which base, sugar and phosphate groups are each represented by one site, our new model incorporates coarse-grained SWCNTs with 2:1 mapping of carbon atoms. The interaction potentials between DNA sites and CNT sites are characterized by standard 12-6 Lennard-Jones potential, for which parameters are based on all-atom MD simulation results, and parameters are differentiated for different bases (A,T,G,C). The simplicity of this model improves computational affordability, while capturing the essential features of DNA-CNT interactions observed from all-atom MD simulations. Employing umbrella sampling, we focus on analyzing the relationship between adsorption free energy and two important parameters, namely, length of the oligonucleotide and SWCNT surface coverage. Results indicate that the absolute value of adsorption free energy increases linearly with the length of oligonucleotides (of the same base type, e.g., T3, T6, T12), and that the free energy for oligonucleotides of the same length are sequence-specific (e.g., T12 versus A12). Analysis of nanotube surface coverage by various oligonucleotides shows that the absolute value of adsorption free energy decreases quadratically with increasing the DNA coverage (the number of strands of pre-adsorbed ssDNA on nanotube), and that the decrease in free energy is dependent on the length and sequence of both the analyte oligonucleotide and pre-adsorbed ssDNAs.