A statistical model for translocation of structured polypeptide chains through nanopores.
The translocation process of a globular protein (ubiquitin) across a cylindrical nanopore is studied via molecular dynamics simulations. The ubiquitin is described by a native-centric model on a Calpha carbon backbone to investigate the influence of protein-like structural properties on the translocation mechanism. A thermodynamical and kinetic characterization of the process is obtained by studying the statistics of blockage times, the mobility, and the translocation probability as a function of the pulling force F acting in the pore. The transport dynamics occurs when the force exceeds a threshold Fc depending on a free-energy barrier that ubiquitin has to overcome in order to slide along the channel. Such a barrier results from competition of the unfolding energy and the entropy associated with the confinement effects of the pore. We implement appropriate umbrella sampling simulations to compute the free-energy profile as a function of the position of the ubiquitin center of mass inside of the channel (reaction coordinate). This free energy is then used to construct a phenomenological drift-diffusion model in the reaction coordinate which explains and reproduces the behavior of the observables during the translocation.
Ammenti
Alessandro
A
Dipartimento di Fisica, Università di Perugia, Via A. Pascoli, 06123 Perugia, Italy.
Cecconi
Fabio
F
Marini Bettolo Marconi
Umberto
U
Vulpiani
Angelo
A
D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009068:Movement; D036103:Nanotechnology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D016062:Porosity; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D025801:Ubiquitin