Design of programmable molecular interfaces for synthetic biology and therapeutic applications.

De novo protein design is reshaping how synthetic biology specifies and controls molecular function. Recent advances in generative modeling, sequence design and structure prediction enable molecular interactions to be created from scratch, reducing reliance on natural solutions and extensive experimental screening. These approaches support the design of compact, stable binding proteins, programmable interaction modules, and higher-order assemblies with defined geometry and regulatory behavior. As a result, de novo proteins are increasingly used to modulate signaling pathways, direct molecular targeting, and organize functional architectures across diverse biological contexts. Although challenges remain in predicting behavior in complex environments and balancing multiple design objectives, continued methodological progress is establishing de novo scaffolds as versatile, composable elements for the next-generation of synthetic biology.