In nanopore force spectroscopy (NFS) a charged polymer is threaded through a channel of molecular dimensions. When an electric field is applied across the insulating membrane, the ionic current through the nanopore reports on polymer translocation, unzipping, dissociation, and so forth. We present a new model that can be applied in molecular dynamics simulations of NFS. Although simplified, it does reproduce experimental trends and all-atom simulations. The scaled conductivities in bulk solution are consistent with experimental results for NaCl for a wide range of electrolyte concentrations and temperatures. The dependence of the ionic current through a nanopore on the applied voltage is symmetric and, in the voltage range used in experiments (up to 2 V), linear and in good agreement with experimental data. The thermal stability and geometry of DNA is well represented. The model was applied to simulations of DNA hairpin unzipping in nanopores. The results are in good agreement with all-atom simulations: the scaled translocation times and unzipping sequence are similar.

When an electric field is applied to an insulating membrane, movement of charged particles through a nanopore is induced. The measured ionic current reports on biomolecules passing through the nanopore. In this work, we explored the kinetics of DNA unzipping in a nanopore using our coarse-grained model (Stachiewicz and Molski, J. Comput. Chem. 2015, 36, 947). Coarse graining allowed a more detailed analysis for a wider range of parameters than all-atom simulations. Dependence of the translocation mode (unzipping or distortion) on the pore diameter was examined, and the threshold voltages were estimated. We determined the potential of mean force, position-dependent diffusion coefficient, and position-dependent effective charge for the DNA unzipping. The three molecular profiles were correlated with the ionic current and molecular events. On the unzipping/translocation force profile, two energy maxima were found, one of them corresponding to the unzipping, and the other to the translocation barriers. The unzipping kinetics were further explored using Brownian dynamics.

By applying an electric field to an insulating membrane, movement of charged particles through a nanopore can be induced. The measured ionic current reports on biomolecules passing through the nanopore. In this paper, we explore the sequence-dependent dynamics of DNA unzipping using our recently developed coarse-grained model. We estimated three molecular profiles (the potential of mean force, position-dependent diffusion coefficient, and positiondependent effective charge) for the DNA unzipping of four hairpins with different sequences. We found that the molecular profiles are correlated with the ionic current and molecular events. We also explored the unzipping kinetics using Brownian dynamics. We found that the effect of hairpin structure on the unzipping/translocation times is not only energetic (weaker hairpins unzip more quickly) but also kinetic (different unzipping and translocation pathways play an important role).