In voltage driven translocation experiments (Kasianowicz et al. 1996), an applied voltage across two electrolytic cells connected through a nanopore induces the migration of macromolecules across the hole. The macromolecule engaging the pore produces detectable ion current variations that can be very informative on the physical and chemical properties of the passing species. While this experimental technique is announced to work for fast and cheap sequencing of nucleic acids, its applicability to protein molecules is still under intensive research.
An increasing accumulation of experimental data supports the view that large proteins translocate across narrow pores via a multistep process involving a sequence of dynamical bottlenecks (stall events) that, to some extent, can be considered as the fingerprint of the passing molecule. Our computer simulations on a coarse-grained model of the protein-pore system confirm the multistep scenario which results from the tight coupling between the unfolding process and the translocation dynamics. Moreover our results strongly indicate a correlation between: i) stall events of the transport dynamics, ii) ascending ramps in the free-energy profile G(Q) of a translocation reaction coordinate Q, and iii) regions of the protein richer in "backward native-contacts" (i.e. native non-bonded interactions among those aminoacids that have not yet entered the pore).
We thus can argue that the sequence and nature of such bottlenecks might have a simple and univocal interpretation in terms of the structural properties of the protein native-state. Therefore, inference on the presence of a multistep translocation dynamics of proteins can be done from the knowledge of their native-state topology. In a possible inverse scenario, we guess that the correlation between stalls and protein structural elements would allow to distinguish protein motives and domains from the detection of stalls during the translocation dynamics.