Protein Interactions as Targeted Therapeutics
Protein–protein interactions between membrane-localized receptors and intracellular signalling molecules regulate neuronal function and, in theory, provide a rich source of drug discovery targets in neuropsychopharmacology. The flat, expanding, and adaptive shape of the protein–protein interface, in contrast to the well-defined binding pocket of transporters and receptors, offers a significant hurdle to the goal of discovering small compounds that cause a gain or loss of function of the protein–protein complex. This is countered by mounting evidence that a few amino acids near the interface ('hot spot') account for the majority of the binding energy in protein–protein interactions, implying that highly targeted modulators could be produced.
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