Computational redesign of protein-protein interaction specificity

TitleComputational redesign of protein-protein interaction specificity
Publication TypeJournal Article
Year of Publication2004
AuthorsKortemme, T., Joachimiak L. A., Bullock A. N., Schuler A. D., Stoddard B. L., & Baker D.
JournalNature structural & molecular biology
Date Published2004 Apr
KeywordsBacterial Proteins, Binding Sites, Computational Biology, Deoxyribonucleases, Kinetics, Models, Molecular, Primary Publication, Protein Structure, Secondary, Proteins, Sensitivity and Specificity

We developed a 'computational second-site suppressor' strategy to redesign specificity at a protein-protein interface and applied it to create new specifically interacting DNase-inhibitor protein pairs. We demonstrate that the designed switch in specificity holds in in vitro binding and functional assays. We also show that the designed interfaces are specific in the natural functional context in living cells, and present the first high-resolution X-ray crystallographic analysis of a computer-redesigned functional protein-protein interface with altered specificity. The approach should be applicable to the design of interacting protein pairs with novel specificities for delineating and re-engineering protein interaction networks in living cells.

Alternate JournalNat. Struct. Mol. Biol.
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