Probing the Disordered Domain of the Nuclear Pore Complex through Coarse-Grained Molecular Dynamics Simulations

Ali Ghavami, Liesbeth M. Veenhoff, Erik van der Giessen, Patrick R. Onck*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

61 Citaten (Scopus)
275 Downloads (Pure)


The distribution of disordered proteins (FG-nups) that line the transport channel of the nuclear pore complex (NPC) is investigated by means of coarse-grained molecular dynamics simulations. A one-bead-per-amino-acid model is presented that accounts for the hydrophobic/hydrophilic and electrostatic interactions between different amino acids, polarity of the solvent, and screening of free ions. The results indicate that the interaction of the FG-nups forms a high-density, doughnut-like distribution inside the NPC, which is rich in FG-repeats. We show that the obtained distribution is encoded in the amino-acid sequence of the FG-nups and is driven by both electrostatic and hydrophobic interactions. To explore the relation between structure and function, we have systematically removed different combinations of FG-nups from the pore to simulate inviable and viable NPCs that were previously studied experimentally. The obtained density distributions show that the maximum density of the FG-nups inside the pore does not exceed 185 mg/mL in the inviable NPCs, whereas for the wild-type and viable NPCs, this value increases to 300 mg/mL. Interestingly, this maximum density is not correlated to the total mass of the FG-nups, but depends sensitively on the specific combination of essential Nups located in the central plane of the NPC.

Originele taal-2English
Pagina's (van-tot)1393-1402
Aantal pagina's10
TijdschriftBiophysical Journal
Nummer van het tijdschrift6
StatusPublished - 16-sep-2014

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