title: Brownian dynamics simulation of nucleocytoplasmic transport: a coarse-grained model for the functional state of the nuclear pore complex.
abstract: The nuclear pore complex (NPC) regulates molecular traffic across the nuclear envelope (NE). Selective transport happens on the order of milliseconds and the length scale of tens of nanometers; however, the transport mechanism remains elusive. Central to the transport process is the hydrophobic interactions between karyopherins (kaps) and Phe-Gly (FG) repeat domains. Taking into account the polymeric nature of FG-repeats grafted on the elastic structure of the NPC, and the kap-FG hydrophobic affinity, we have established a coarse-grained model of the NPC structure that mimics nucleocytoplasmic transport. To establish a foundation for future works, the methodology and biophysical rationale behind the model is explained in details. The model predicts that the first-passage time of a 15 nm cargo-complex is about 2.6±0.13 ms with an inverse Gaussian distribution for statistically adequate number of independent Brownian dynamics simulations. Moreover, the cargo-complex is primarily attached to the channel wall where it interacts with the FG-layer as it passes through the central channel. The kap-FG hydrophobic interaction is highly dynamic and fast, which ensures an efficient translocation through the NPC. Further, almost all eight hydrophobic binding spots on kap-β are occupied simultaneously during transport. Finally, as opposed to intact NPCs, cytoplasmic filaments-deficient NPCs show a high degree of permeability to inert cargos, implying the defining role of cytoplasmic filaments in the selectivity barrier.
authors.affiliation: Molecular Cell Biomechanics Laboratory, Department of Bioengineering, University of California, Berkeley, California, United States of America.
authors.forename: Ruhollah
authors.initials: R
authors.lastname: Moussavi-Baygi
authors.forename: Yousef
authors.initials: Y
authors.lastname: Jamali
authors.forename: Reza
authors.initials: R
authors.lastname: Karimi
authors.forename: Mohammad R K
authors.initials: MR
authors.lastname: Mofrad
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D055119:Elastic Modulus; D057927:Hydrophobic and Hydrophilic Interactions; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D022022:Nuclear Pore / Q000737:chemistry* / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D009865:Oocytes; D017434:Protein Structure, Tertiary; D014783:Viscosity; D014981:Xenopus
chemical_list: D029543:Nucleocytoplasmic Transport Proteins