De Novo Design of Inhibitors of Protein-Protein Interactions
Protein-protein interactions play critical roles in biology both inside and outside cells. However it is currently difficult to probe the importance of specific intracellular protein-protein interactions at a particular developmental stage and location, or in a particular cell type. Few protein-protein interfaces can be disrupted with small molecules, and even where available, it is very difficult to deliver small molecules to specific tissues. Extracellular protein-protein interactions can be probed using antibodies that disrupt the interface by competition, but it is difficult to deliver antibodies inside cells. Whole proteins can be eliminated by gene knockouts, but this does not allow interrogation of the importance of individual interactions made by one domain in a modular multidomain protein. This project will use the Rosetta protein design methodology to arrive at de novo designed protein inhibitors of protein-protein interactions.