Protein translocation in narrow pores: Inferring bottlenecks from native structure topology

Coarse-grained simulations of protein translocation across narrow pores suggest that the transport is characterized by long stall events. The translocation bottlenecks and the associated free-energy barriers are found to be strictly related to the structural properties of the protein native structure. The ascending ramps of the free-energy profile systematically correspond to regions of the chain denser in long range native contacts formed with the untranslocated portion of the protein. These very regions are responsible for the stalls occurring during the protein transport along the nanopore. The decomposition of the free energy in internal energy and entropic terms shows that the dominant energetic contribution can be estimated on the base of the protein native structure only. Interestingly, the essential features of the dynamics are retained in a reduced phenomenological model of the process describing the evolution of a suitable collective variable in the associated free-energy landscape.