Fast and selective transportation of macromolecules between the cytoplasm and the nucleoplasm is essential for the proper functioning of eukaryotic cells. This is accomplished by the nuclear pore complex (NPC), a large molecular protein assembly in the nuclear membrane. It is generally accepted that nuclear transport is controlled by unfolded proteins (FG-nups) that line the central channel of the NPC. However, how the biophysical properties of the FG-nups mediate transport is not well understood.

One of the reasons that have hampered the understanding of nuclear transport is the absence of experimental techniques that can probe the structure of the FG-nups inside the transport channel. This has led to the development of computational approaches to gain insight on the conformation of the FG-nups inside the NPC and their role in transport. Due to the large size of the system, high-resolution (all-atom) molecular dynamics simulations are restricted to study only a limited number of FG-nups. On the other hand, several low-resolution approaches have been used to study transport, but at the expense of losing detail at the scale of individual amino acids.

The goal of this work is to probe the full three-dimensional disordered domain of the yeast NPC by accounting for all FG-nups, each having a complete 20 amino-acid resolution. To bridge the gap between the scale of individual amino acids and the scale of the full NPC, we have developed a one-bead-per-amino-acid molecular dynamics model. The model captures the bonded interactions of the atomistic polypeptide chain as well as the non-bonded electrostatic and hydrophobic interactions between different aminoacids. I will discuss some recent results on the predicted spatial conformation of the FG-nups and their energy barrier and how this is encoded in the amino-acid sequence.