(387g) Alcohol Effects On Trans Nuclear Membrane Transport

The nuclear pore complex (NPC) provides a size-selective transport barrier that regulates traffic between the nucleus and cytoplasm. Intrinsically disordered phenylalanine-glycine nucleoporins (FG-Nups) serve as the barrier to transport through the central pore of the NPC. Experimentally it has been observed that alcohols of increasing hydrophobic reversibly diminish the permeability barrier, suggesting the hydrophobic side chains of the FG-Nups microphase separate to form a mesh-like gel that sieves large species. Using molecular simulations, we investigate the solvent-mediated interactions between hydrophobic FG-Nup side chains and the effect of alcohols. Alcohols of increasing hydrophobicity are found to induce side-chain aggregation, in difference to the interpretation that alcohols disperse these amino acids. Our simulations suggest that the decreased selectivity is a result of holes opening within the FG-Nup mesh, providing pathways for trans nuclear membrane transport.