Computational and theoretical insights into protein and peptide translocation

Biological processes such as protein degradation and mitochondrial protein import require protein passage, or translocation, across narrow pores. In addition to its biological significance, protein translocation through biological or engineered nanopores offers a powerful analytic tool for biophysics and nanotechnology. This mini-review discusses the physical mechanisms of protein translocation, as revealed by computational and theoretical studies. A simple, simulation-based model of translocation is presented, which provides a comprehensive description of this process and allows one to estimate experimentally observable quantities such as the dwell time of a protein inside the pore and the frequency of translocation events. Limitations of this model are further described and possible strategies to overcome them are outlined. Recent simulation studies are beginning to provide insights into the physical mechanisms that drive protein translocation in living systems, which are also discussed here.