Computational Drug Design Targeting Protein-Protein Interactions

Curr Pharm Des. 2012;18(9):1240-54. doi: 10.2174/138161212799436449.


Novel discoveries in molecular disease pathways within the cell, combined with increasing information regarding protein binding partners has lead to a new approach in drug discovery. There is interest in designing drugs to modulate protein-protein interactions as opposed to solely targeting the catalytic active site within a single enzyme or protein. There are many challenges in this new approach to drug discovery, particularly since the protein-protein interface has a larger surface area, can comprise a discontinuous epitope, and is more amorphous and less well defined than the typical drug design target, a small contained enzyme-binding pocket. Computational methods to predict modes of protein-protein interaction, as well as protein interface hot spots, have garnered significant interest, in order to facilitate the development of drugs to successfully disrupt and inhibit protein-protein interactions. This review summarizes some current methods available for computational protein-protein docking, as well as tabulating some examples of the successful design of antagonists and small molecule inhibitors for protein-protein interactions. Several of these drugs are now beginning to appear in the clinic.

Publication types

  • Review

MeSH terms

  • Animals
  • Computer-Aided Design*
  • Drug Delivery Systems
  • Drug Design*
  • Drug Discovery / methods
  • Humans
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Interaction Mapping / methods
  • Proteins / chemistry
  • Proteins / metabolism*


  • Proteins