Residue-based pharmacophore approaches to study protein-protein interactions

Curr Opin Struct Biol. 2021 Apr:67:205-211. doi: 10.1016/ Epub 2021 Jan 22.


This review focuses on pharmacophore approaches in researching protein interfaces that bind protein ligands. Pharmacophore descriptions of binding interfaces that employ molecular dynamics simulation can account for effects of solvation and conformational flexibility. In addition, these calculations provide an approximation to entropic considerations and as such, a better approximation of the free energy of binding. Residue-based pharmacophore approaches can facilitate a variety of drug discovery tasks such as the identification of receptor-ligand partners, identifying their binding poses, designing protein interfaces for selectivity, or defining a reduced mutational combinatorial exploration for subsequent experimental engineering techniques by orders of magnitudes.

Publication types

  • Review

MeSH terms

  • Binding Sites
  • Drug Discovery*
  • Ligands
  • Molecular Conformation
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Protein Binding*
  • Protein Interaction Maps


  • Ligands