14. Nanopore Force Spectroscopy: Insights from Molecular Dynamics Simulations

Nanopore force spectroscopy (NFS) has emerged as a convenient method to characterize the behavior of single biomolecules and biomolecular assemblies under force. NFS has many advantages over conventional single molecule techniques, such as being label-free and high throughput; however, NFS lacks direct control over the force applied to the biomolecules and registers the conformational transitions induced by the force only indirectly, by monitoring changes in the ionic current passing through the pore. In this chapter, we describe how all-atom molecular dynamics simulations can complement NFS experiments by providing information inaccessible to experiment. The chapter illustrates applications of the molecular dynamics (MD) method to interpret the results of NFS measurements, characterize the forces involved and determine the microscopic origin of the observed phenomena. Important technical aspects of the method, as well as its pitfalls and limitations are briefly discussed.