Design principles of protein switches

Protein switches perform essential roles in many biological processes and are exciting targets for de novo protein design, which aims to produce proteins of arbitrary shape and functionality. However, the biophysical requirements for switch function - multiple conformational states, fine-tuned energetics, and stimuli-responsiveness - pose a formidable challenge for design by computation (or intuition). A variety of methods have been developed toward tackling this challenge, usually taking inspiration from the wealth of sequence and structural information available for naturally occurring protein switches. More recently, modular switches have been designed computationally, and new methods have emerged for sampling unexplored structure space, providing promising new avenues toward the generation of pur pose-built switches and de novo signaling systems for cellular engineering.

Automated summary

Protein switches play essential roles in biological processes and are challenging to design computationally due to their complex requirements. Inspired by natural protein switches, various methods have been developed to overcome this challenge and explore new ways to design purpose-built switches and signaling systems for cellular engineering.