Structural Integrity of ssDNA on the Surface of Solid-state Nanopores

Self-assembly and 3D conformation of nucleic acid aptamers enable selective binding with biomarkers and cells. One mode of utilizing selective property of the aptamers is by grafting these in solid-state nanopores. Coating the inside walls of the nanopores with protein specific nucleic acid aptamers changes the energy landscape and affects the biomarker translocation. When the target protein passes through the nanopore, it interacts with surface-bound DNA and the process alters overall energy profile, which is essentially specific to the protein detected. The simulations showed that fundamental challenges in this process were to ensure these detection motifs held their structure and functionality under applied electric field and experimental conditions. The all-atom molecular dynamics simulation of the effects of external electric field on the 3D conformation of such ligand-DNA demonstrated how the grafted moieties affected the translocation time, velocity and the detection frequency of the target molecule. A novel case of protein translocation was also investigated for comparison where DNA was pre-bound to the protein.