All-Atom Molecular Dynamics Simulation of Protein Translocation through an α-Hemolysin Nanopore


Di Marino, Daniele
Bonome, Emma Letizia
Tramontano, Anna
Chinappi, Mauro

KAUST Grant Number

Online Publication Date

Print Publication Date


© 2015 American Chemical Society. Nanopore sensing is attracting the attention of a large and varied scientific community. One of the main issues in nanopore sensing is how to associate the measured current signals to specific features of the molecule under investigation. This is particularly relevant when the translocating molecule is a protein and the pore is sufficiently narrow to necessarily involve unfolding of the translocating protein. Recent experimental results characterized the cotranslocational unfolding of Thioredoxin (Trx) passing through an α-hemolisin pore, providing evidence for the existence of a multistep process. In this study we report the results of all-atom molecular dynamics simulations of the same system. Our data indicate that Trx translocation involves two main barriers. The first one is an unfolding barrier associated with a translocation intermediate where the N-terminal region of Trx is stuck at the pore entrance in a conformation that strongly resembles the native one. After the abrupt unfolding of the N-terminal region, the Trx enters the α-hemolisin vestibule. During this stage, the constriction is occupied not only by the translocating residue but also by a hairpin-like structure forming a tangle in the constriction. The second barrier is associated with the disentangling of this region.

Di Marino D, Bonome EL, Tramontano A, Chinappi M (2015) All-Atom Molecular Dynamics Simulation of Protein Translocation through an α-Hemolysin Nanopore. The Journal of Physical Chemistry Letters 6: 2963–2968. Available:

This research used the computational resource of the Supercomputing Laboratory at King Abdullah University of Science & Technology (KAUST) in Thuwal, Saudi Arabia and of the CINECA (GRAPUNA project) and PRACE project 2014112673. Funding: KAUST Award No. KUK-I1-012-43 made by King Abdullah University of Science and Technology (KAUST).

American Chemical Society (ACS)

The Journal of Physical Chemistry Letters


PubMed ID

Permanent link to this record