17 Mar 2021
The Journal of biological chemistry; - :
Computational de novo protein design is increasingly applied to address a number of key challenges in biomedicine and biological engineering. Successes in expanding applications are driven by advances in design principles and methods over several decades. Here, we review recent innovations in major aspects of de novo protein design, and include how these advances were informed by principles of protein architecture and interactions derived from the wealth of structures in the PDB. We describe developments in de novo generation of designable backbone structures, in optimization of sequences, in design scoring functions, and in design of function. The advances not only highlight design goals reachable now but also point to the challenges and opportunities for the future of the field.