De novo design of transmembrane nanopores

Transmembrane nanopores are structurally stable and biocompatible, and have various applications in molecular sensing and selective transport. The relationship between the function and structure is crucial for transmembrane nanopores, but it is still challenging to design and precisely tune the structure of conventional protein nanopores from scratch, albeit of abundant previous work on natural and bioengineered transmembrane protein nanopores. Therefore, numerous types of artificial transmembrane nanopores that can be de novo designed are rapidly under development, such as molecular nanopores, peptide nanopores, and DNA origami nanopores. In this review, we compare different building blocks of “bottom-up” built nanopores in terms of construction methods, structures and applications, and also describe important advances in de novo designed proteins from the perspective of theoretical simulations as well as an outlook for artificial intelligence-assisted nanopore design.