Data-driven design of orthogonal protein-protein interactions.

ABSTRACT: Engineering protein-protein interactions to generate new functions presents a challenge with great potential for many applications, ranging from therapeutics to synthetic biology. To avoid unwanted cross-talk with preexisting protein interaction networks in a cell, the specificity and selectivity of newly engineered proteins must be controlled. Here, we developed a computational strategy that mimics gene duplication and the divergence of preexisting interacting protein pairs to design new interactions. We used the bacterial PhoQ-PhoP two-component system as a model system to demonstrate the feasibility of this strategy and validated the approach with known experimental results. The designed protein pairs are predicted to exclusively interact with each other and to be insulated from potenti

SUBMITTER: Malinverni D 

PROVIDER: S-EPMC7614567 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature