Protein Interactions as Targeted Therapeutics
Protein–protein interactions between membrane-localized receptors and intracellular signalling molecules control neuronal function and theoretically provide a rich source of vastly excluded targets for drug discovery in neuropsychopharmacology. But, unlike the well-defined binding pocket of transporters and receptors, the flat, expansive, and adaptive topology of the protein–protein interface presents a sizeable challenge to the goal of identifying small molecules that result in a gain or loss of function of the protein-protein complex. This is offset by the growing body of evidence to suggest that a few amino acids at the interface (‘hot spot’) contribute to the majority of the binding energy in protein–protein interactions suggesting that modulators with a high degree of specificity could be developed. Furthermore, recent approaches in screening technologies and accessibility to an ever-increasing diversity of small molecules propose that protein–protein interactions are a viable option for drug discovery.