  At the molecular level, most biological processes entail protein associations
which in turn rely on a small fraction of interfacial residues called hot
spots. Here we show that hot spots share a unifying molecular attribute: they
provide a third-body contribution to intermolecular cooperativity. Such motif,
based on the wrapping of interfacial electrostatic interactions, is essential
to maintain the integrity of the interface and can be exploited in rational
drug design since such regions may serve as blueprints to engineer small
molecules disruptive of protein-protein interfaces.
