Dekker, M.; de Vries, H. W.; Wortelboer, K. A.; Beekhuis, H. J.; Van der Giessen, E.; Onck, P. R.

Recent studies of nuclear pore complexes (NPCs) have provided detailed descriptions of the core scaffold structures, yet fall short in resolving the dynamic FG-meshwork with similar precision. Here, we present a novel modeling framework that enables the simulation of nuclear transport at full amino-acid resolution. We describe the distributions of the different FG-Nups in the central transporter and highlight the dynamic nature of the FG-meshwork, with FG-FG interaction lifetimes on the order of nanoseconds. Our findings reveal that Nsp1, the most abundant FG-Nup in the NPC, creates a central meshwork due to its unique bimodal structure, that is essential for controlling both passive and active transport. By introducing nuclear transport receptors (NTRs) - in the form of Kap95 - to the pore, we demonstrate that NTRs play a key role in increasing the energy barrier for translocation of inert particles. We observe a dynamic interplay between high affinity binding to FG-motifs and the temporal fluctuations of the FG-meshwork, leading to local low-density pockets, so-called voids, through which Kaps move. Furthermore, we show that the introduction of Kaps to the FG-meshwork results in a clear \"dirty velcro\" mechanism with slower Kaps decorating the sticky surface of the high-density GLFG-assembly, thus enabling fast translocation of Kaps through the center of the pore.