Base- and Structure-Dependent DNA Dinucleotide–Carbon Nanotube Interactions: Molecular Dynamics Simulations and Thermodynamic Analysis

Abstract

Wrapping of single-wall carbon nanotubes (SWCNTs) by single-stranded DNA (ssDNA) was found to be sequence-dependent, offering properties such as the facilitation of SWCN sorting, ultrafast DNA sequencing, and construction of chemical sensors. Although the interactions of nucleic acids with SWCNTs have been studied thoroughly, the DNA–CNT hybrid especially for the oligonucleotides containing more than one nucleotide has not yet been fully understood. To address this, we have examined new and unconventional DNA dinucleotides involving all 16 combinations of two DNA nucleotides attached with chiral (8,4) and armchair (6,6) SWCNTs using all-atom molecular dynamics simulations and thermodynamic analyses. The 16 dinucleotides with different sequence compositions are found to readily adsorb onto SWCNTs and display interesting binding behaviors such as base flipping, local dynamic stability of structure, and conformational shifting. Four dinucleotides, i.e., AC, AG, GC, and GT, share similar dynamic properties (base turning and conformation transformation) in (8,4) and (6,6) systems. The different dynamic profiles between the compositional isomers with the reverse sequences such as the AG and GA show that the sequence order also impacts the dynamic recognition and binding energy of the ssDNA–CNT hybrid. Clustering-analysis-derived representative conformations imply that general dinucleotides are inclined to spread on the SWCNT surface, and the adjacent bases tend to stretch away from each other. Dinucleotides like AC, AT, CG, CT, GC, GG, TA, TC, TG, and TT adopt similar geometries on both CNTs, suggesting that their structures are not predominantly influenced by the nanotube chirality but controlled by the identity of the base sequence, sequence order, and the basic cylindric structure of SWCNT. In addition, the nucleotide bases have a high degree of orientational order on the nanotube surface and the orientations of each base are significantly affected by the sequence of DNA and the chirality of nanotube, emphasizing that the structural order plays an important role in the binding of DNA and CNTs. However, our energy analysis shows that due to small different curvatures of the CNT surface, the binding affinity of most dinucleotides (except AG, CA, CG, and TG) to the chiral and armchair nanotube is not significantly different. Generally, the dinucleotides constituted with purine and thymine exhibit the lowest binding free energy, resulting from the van der Waals interactions and solvent effects. The thymine-based dinucleotides reduce the solvation free energy of the SWCNT in aqueous solution more effectively as compared to other bases. The present work also demonstrates that the total binding free energy is sequence specific but not merely a sum of individual base–SWCNT binding free energies.