Discovering molecules that modulate protein-protein interactions is challenging, because the protein interfaces generally lack recognizable binding sites. Pennsylvania State University chemist Stephen Benkovic and colleagues have now developed a high-throughput technique that can identify rare inhibitors of these interactions. These molecules could be used as pharmaceutical lead compounds and probes of intracellular networks, Benkovic says, noting that Rigel Pharmaceutical in San Francisco has licensed the system for work in eukaryotes.