Structure-based druggability assessment--identifying suitable targets for small molecule therapeutics

Curr Opin Chem Biol. 2011 Aug;15(4):463-8. doi: 10.1016/j.cbpa.2011.05.020. Epub 2011 Jun 23.


A target is druggable if it can be modulated in vivo by a drug-like molecule. The general properties of oral drugs are summarized by the 'rule of 5' which specifies parameters related to size and lipophilicity. Structure-based target druggability assessment consists of predicting ligand-binding sites on the protein that are complementary to these drug-like properties. Automated identification of ligand-binding sites can use geometrical considerations alone or include specific physicochemical properties of the protein surface. Features of a pocket's size and shape, together with measures of its hydrophobicity, are most informative in identifying suitable drug-binding pockets. The recent availability of several validation sets of druggable versus undruggable targets has helped fuel the development of more elaborate methods.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Binding Sites
  • Drug Design*
  • Drug Evaluation, Preclinical / methods
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Models, Molecular*
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism
  • Protein Binding
  • Proteins / chemistry*
  • Proteins / metabolism
  • Quantitative Structure-Activity Relationship*
  • Small Molecule Libraries / chemistry*


  • Ligands
  • Pharmaceutical Preparations
  • Proteins
  • Small Molecule Libraries