Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein-Protein Interactions.

ABSTRACT: Protein-protein interactions (PPIs) and protein-metabolite interactions play a key role in many biochemical processes, yet they are often viewed as being independent. However, the fact that small molecule drugs have been successful in inhibiting PPIs suggests a deeper relationship between protein pockets that bind small molecules and PPIs. We demonstrate that 2/3 of PPI interfaces, including antibody-epitope interfaces, contain at least one significant small molecule ligand binding pocket. In a representative library of 50 distinct protein-protein interactions involving hundreds of mutations, >75% of hot spot residues overlap with small molecule ligand binding pockets. Hence, ligand binding pockets play an essential role in PPIs. In representative cases, evolutionary unrelated monomers tha

SUBMITTER: Skolnick J 

PROVIDER: S-EPMC9484464 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature