In our lab, we engineer inhibitors of protein-protein interactions starting from natural binding partners as well as from unrelated small protein domains. Recent studies have proven a fantastic potential of protein-based inhibitors derived from natural effectors or unrelated small protein scaffolds. Such inhibitors could be evolved to selectively target only one family member among hundreds of homologs, making them attractive drug candidates. Using the computational methodology developed in our lab, we design mutations that convert the natural low-affinity binding partners into high-affinity and high-specificity binders. In addition, using computational and experimental methods, we engineer novel binders for various target proteins. Our approaches are universal and could be applied to design therapeutics for any disease where a known protein-protein interaction plays a crucial role.