Computational Methods Applicable to the Discovery of Small-Molecule Inhibitors of Protein-Protein Interactions

Protein-protein interactions (PPIs) play a vital role in directing various life processes and are responsible for both normal and aberrant cellular functions. Thus, PPIs serve as a large family of potential targets for drug discovery, which are yet to be fully explored. Due to the unique nature of PPIs, as well as certain technical difficulties, they are considered to be challenging targets for drug discovery. However, in the past two decades or so, significant progress has been made in both experimental and computational techniques applicable to this subject, and these developments have accelerated advances in the field. In this chapter, we review several typical computational methods that can be used for discovering small-molecule inhibitors of PPIs. In addition, several representative studies published in recent years in which these computational methods have been applied to the discovery of PPI inhibitors are briefly described.