Molecular dynamics simulations of transport selectivity in native and artificial nuclear pore complexes

It is vitally important that eukaryotic cells maintain control over the traffic of molecules from and to the cell nucleus, since that is where a cell’s genetic material (DNA) is stored. Nuclear pores, openings in the nuclear membrane, carry out this function. Nuclear pores consist of hundreds of proteins: these form a ring-shaped structure, lined on the inside with very flexible proteins (FG-Nups). Small molecules move past the FG-Nups freely, but larger molecules need to be accompanied by a transport protein to enter or leave the cell nucleus. No consensus has been reached yet on the exact mechanisms behind this selectivity.

In his thesis, Henry de Vries provides new insights into the selective transport function of nuclear pores via molecular dynamics (MD) simulations. De Vries first focused on (simulations of) artificial nuclear pores, which can be created by coating nanopores with FG-Nups and are easier to study experimentally than native nuclear pores. The simulations offer new explanations for the existence of fast and slowly moving populations of transport proteins and how these proteins distribute among FG-Nups. Moreover, simulations of designer FG-Nups reveal how the amino acid sequence of FG-Nups plays a critical role in the emergence of transport selectivity.

Furthermore, De Vries describes a simulation model of a yeast nuclear pore and methods to extend this model with all relevant transport proteins. He concludes by combining all findings into a consensus mechanism for transport selectivity and recommendations for future research, where developments in nanopore technology and AI play important roles.

See also: ‘Designer’ pore shows selective traffic to and from the cell nucleus

Dissertation: https://hdl.handle.net/11370/92e01c51-ef1f-4e92-a38e-e490c93e10b1