Engineering conditional protein-protein interactions for dynamic cellular control

Conditional protein-protein interactions enable dynamic regulation of cellular activity and are an attractive approach to probe native protein interactions, improve metabolic engineering of microbial factories, and develop smart therapeutics. Conditional protein-protein interactions have been engineered to respond to various chemical, light, and nucleic acid-based stimuli. These interactions have been applied to assemble protein fragments, build protein scaffolds, and spatially organize proteins in many microbial and higher-order hosts. To foster the development of novel conditional protein-protein interactions that respond to new inputs or can be utilized in alternative settings, we provide an overview of the process of designing new engineered protein interactions while showcasing many recently developed computational tools that may accelerate protein engineering in this space.