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Protein-Protein Interaction Library

Protein-Protein Interaction Library

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•Protein-protein interactions (PPIs) represent a vast class of therapeutic targets both inside and outside the cell
•Protein–protein interactions (PPIs) are involved in most cellular processes and influence biological functions - enzymatic activity, subcellular localization, and/or binding properties
•The human interactome has been estimated to cover ~400,000 protein–protein interactions
•High-resolution structures showed PPI interfaces are generally flat and large (roughly 1000–2000 A2 per side) and considered difficult to target
•Mutational analysis of protein interfaces showed that not all residues at the PPI interface were critical but rather small “hot spots” conferred most of the binding energy (Arkin and Wells, 2004; Clackson and Wells, 1995). Hot spots tended to cluster at the center of the interface, to cover an area comparable to the size of a small molecule, to be hydrophobic, and to show conformational adaptivity
•Modulation of PPIs provide a wealth of opportunities for therapeutic intervention in a broad range of disease conditions

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