Rationale in Custom Design of Transmembrane β-Barrel Pores

Biological nanopores incorporated into synthetic membranes are widely used for single-molecule analytical applications such as DNA sequencing. The ability to engineer custom membrane proteins with a pore would allow the generation of a multitude of nanopores for the sensing/sequencing of small molecules and (bio)polymers. The de novo design of transmembrane β-barrel pores has recently enabled the generation of nanopores with custom size, shape, and properties. In this chapter, I describe the rationale of transmembrane β-barrel design and computational methods to assemble the backbones, design sequences, and select the designs for experimental validation.