Kap-centric Nsp1-mediated nuclear transport at full amino acid resolution.

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 an amino acid resolution model that enables full-scale simulations of selective transport through the NPC. We map the spatial distributions and nanosecond dynamics of individual FG-Nups in the central transporter, revealing that the bimodal architecture of Nsp1 forms a dynamic central meshwork essential for regulating both passive and active transport. Incorporating nuclear transport receptors (NTRs), specifically Kap95, shows that NTRs strengthen the permeability barrier by increasing the energetic cost of inert cargo translocation. Kaps exhibit alternating phases of binding and motion, moving through transient voids generated by FG fluctuations. Overall, our simulations identify a dense GLFG-ring coated by low-mobility Kaps and a dynamic central FG meshwork that together create a reduced-dimensional transport surface of optimal binding avidity that drives Kap translocation.