Computational design of transmembrane proteins

In recent decades, major progress has been made in the design of water-soluble proteins, yet the design of transmembrane proteins has lagged considerably. Despite their biological and pharmaceutical importance, only a limited number of transmembrane proteins have been successfully designed owing to the complexity of the membrane environment and difficulties in experimental characterization. Here, we introduce principles for transmembrane protein design in general and discuss design examples, including scaffold proteins and functional proteins. We also discuss how developments in design methods have advanced the field and what we may achieve with recent breakthroughs in structural biology.