Predicting druggable binding sites at the protein-protein interface.

Protein-protein interfaces are highly attractive targets for drug discovery because they are involved in a large number of disease pathways where therapeutic intervention would bring widespread benefit. Recent successes have challenged the widely held belief that these targets are 'undruggable'. The pocket finding algorithms described here show marked differences between the binding pockets that define protein-protein interactions (PPIs) and those that define protein-ligand interactions (PLIs) of currently marketed drugs. In the case of PPIs, drug discovery methods that simultaneously target several small pockets at the protein-protein interface are likely to increase the chances of success in this new and important field of therapeutics.