The nuclear pore complex as an entropic gate: theory and simulation

TL;DR

This paper models the nuclear pore complex's selectivity using polymer physics, showing that a specific block copolymer arrangement explains size selectivity and predicting a linear free energy barrier increase with protein size.

Contribution

It introduces a novel polymer model of the nuclear pore complex that explains its size selectivity, supported by simulations and biochemical consistency.

Findings

Block copolymer arrangement matches biochemical data

Size selectivity explained by entropic effects

Free energy barrier increases linearly with protein size

Abstract

Protein chains of the (FG)$_n$ ($n \simeq$ 300) type cap the cytoplasmatic side of the nucleopore complex, which connects the nucleus to the remainder of an eukaryotic cell. We study the properties of three fundamental polymer models that represent these filaments using Monte Carlo computer simulations. Random walks and the worm like chain model cannot account for the unusual size selectivity of the pore, while a two-dimensional arrangement of intrinsically disordered block copolymers with a high content of $\alpha$-helices is in agreement with the biochemical findings. We predict a linear increase of the free energy barrier of protein transport through the pore with increasing protein diameter, which can be probed experimentally using atomic force microscopy or optical tweezers.