Protein-protein interaction (PPI) (PPI)

Protein-protein interactions (PPIs) are the physical contacts established between two or more protein molecules as a result of biochemical events steered by electrostatic forces and the hydrophobic effect (Nature Reviews Drug Discovery, 2014). These interactions are fundamental to virtually every biological process, including signal transduction, metabolic pathways, and cellular structural integrity (PubMed, PMID: 24511127). In many diseases, such as cancer and neurodegeneration, PPIs are often dysregulated, leading to aberrant signaling or the formation of toxic aggregates (NIH, 2021). Historically considered 'undruggable' due to their large, flat, and featureless interfaces, PPIs have become a major focus of modern drug discovery (StatPearls, 2023). Therapeutic strategies involve the use of small molecules, peptides, or antibodies to either inhibit or stabilize these complexes (PubMed, PMID: 31065015). Successful examples include the BCL-2 inhibitor venetoclax, which disrupts the interaction between pro-apoptotic and anti-apoptotic proteins to induce cell death in leukemia (FDA, 2016). The vast network of these interactions, known as the interactome, offers a rich source of potential therapeutic targets for a wide range of human diseases (Wikipedia, 2024).

Other names

Protein-protein complexInteractomeProtein-protein interface

Inhibition or stabilization of the physical interface between two or more proteins to modulate biological signaling pathways (Nature Reviews Drug Discovery, 2014).