Engineering a handshake for proteins
Once considered undruggable, chemists are beginning to grasp protein–protein interactions, according to Ian Le Guillou
Proteins rarely work alone. From tightly bound complexes to passing transitory contacts, interactions between proteins play a central role in the function of the cell, from regulating gene transcription to metabolism.
By one estimate, there are over 650,000 protein–protein interactions in the human body. This overwhelming array of interactions represents an almost untapped resource of targets for new therapeutic drugs.
For many decades, these interactions were considered to be ‘undruggable’. High-resolution structures of protein–protein interactions (PPIs) in the 1980s and 90s showed that the interfaces were large, flat featureless surfaces. This was entirely different from the deep pockets found in typical drug targets, such as enzymes and receptors, where small molecules can easily bind.