Molecular determinants of selective transport through the nuclear pore complex: a computational study
Nuclear pore complexes (NPCs) are the gatekeepers of the cell nucleus. These massive, ring-shaped structures are filled with flexible, unstructured proteins known as FG-Nups. They act as a selective barrier: while small molecules can pass through freely, the passage of larger molecules is drastically slowed down. To achieve timely entry, large molecules must be escorted by specific carriers called nuclear transport receptors (NTRs). Despite decades of research, the precise physical mechanism underlying this selective gatekeeping remains a subject of scientific debate.
In his thesis, Ankur Mishra uses of molecular dynamics simulations to study transport selectivity in both biological yeast NPCs and biomimetic (artificial) NPCs. Mishra shows that selectivity relies on an intricate balance between hydrophobicity and charge, and can be understood as a dual mechanism: (i) the hydrophobicity of FG-Nups effectively maintains the barrier resisting against passive diffusion, and (ii) charge acts as the key driver for active transport with hydrophobicity playing a supporting role. Mishra demonstrates that hydrophobicity builds the barrier of the gate, while electric charge empowers authorized carriers to pass through.