Conformational Dynamics of the Nuclear Pore Complex: Insights from Elastic Network Models and Coarse-Grained Simulations

The nuclear pore complex (NPC) serves as the primary channel regulating nucleocytoplasmic transport in eukaryotic cells. In recent years, atomic-resolution structural models of both the constricted and dilated states of the NPC central core have been resolved; however, the molecular mechanisms underlying the transition between these two states remain unclear. This study employed elastic network models (ENM) to identify the first three low-frequency collective motion modes of the NPC scaffold structure, revealing the intrinsic relationship between these modes and the two-state transition of the NPC scaffold. Molecular dynamics (MD) simulations were further utilized to achieve dynamic conformational transitions between the constricted and dilated states of the NPC scaffold, providing detailed insights into the dynamics of this process. Regarding the FG repeat sequences within the nuclear pore channel, simulations based on the inner ring heterotrimeric FG-Nups revealed significant differences in their distribution between the constricted and dilated states. Finally, by integrating multi-scale research findings, we propose a potential nucleocytoplasmic transport regulatory pathway that encompasses both NPC conformational changes and FG barrier dynamic behavior, providing novel support and validation for the dilation model.