Protein–Protein Interactions (PPIs) constitute a promising class of targets for drug discovery. Inhibitors
of these original interactions are certainly the next generation of highly innovative drugs that will reach the market
in the next decade. However, the in silico design of such compounds still remains challenging. This review
describes this particular protein-protein interaction chemical space and the main biophysical reasons that make
them challenging targets for the drug discovery process. A state of the art of protein databases and servers
dedicated to PPIs, their analysis and inhibition is also surveyed. It then presents some innovative methodologies
that led to the development of new inhibitors. Finally, different families of protein-protein interactions for which
an inhibitor is known are briefly introduced and potential tracks for the future are proposed such as a new
classification based on protein-protein interfaces with known inhibitors into specific families, with a subsequent
notion of focused databases dedicated to each specific class.
Keywords: protein-protein interactions, protein-protein interfaces, PPIs, 2P2I, drug design, inhibitor, small
molecule, structural databases, druggable target.
