A coarse-grained molecular dynamics model for unfolded proteins in nuclear pores
Ali Ghavami (University of Groningen), Erik Van der Giessen (University of Groningen), Patrick Onck (University of Groningen)
From Atomistics to Reality: Spanning Scales in Simulations and Experiments Symposium A
Tue 9:00 - 10:30
CIT 165
The nuclear pore complex (NPC) is a large protein complex that is embedded in the nuclear membrane of eukaryotic cells and transports hundreds of proteins per second. Despite the wide variety of molecules transported, the NPC is highly selective. It only allows small molecules and ions to freely diffuse in and out of the nucleus; larger proteins are excluded. The actual transport is mediated by natively unfolded proteins that are rich in phenylalanine (F) and glycine (G). These FG-nucleoporins (FG-nups) form a low-density region of flexible filaments that line the core of the NPC. How these FG-nups govern transport is a subject of intense debate. In order to gain insight on the spatial FG-nup conformation in the NPC it is essential to bridge the gap between the atomistic scale of individual amino-acids and the overall scale of the nuclear pore complex. To do so, we propose a one-bead-per -amino acid molecular dynamics (AA-MD) model which accounts for the hydrophobic/hydrophilic and electrostatic interactions between different amino acids, polarity of the solvent and screening of free ions. The force-field is calibrated to experimentally-obtained Stokes radii of FG-nup segments and then used to study the collective behavior of FG-Nups inside the transfer channel. The obtained density plots reveal a unique distribution of charged and hydrophobic residues inside the NPC. In addition, we show that these distributions are encoded in the specific amino-acid sequence of the FG-Nups.