Allostery in disease and in drug discovery

Cell. 2013 Apr 11;153(2):293-305. doi: 10.1016/j.cell.2013.03.034.


Allostery is largely associated with conformational and functional transitions in individual proteins. This concept can be extended to consider the impact of conformational perturbations on cellular function and disease states. Here, we clarify the concept of allostery and how it controls physiological activities. We focus on the challenging questions of how allostery can both cause disease and contribute to development of new therapeutics. We aim to increase the awareness of the linkage between disease symptoms on the cellular level and specific aberrant allosteric actions on the molecular level and to emphasize the potential of allosteric drugs in innovative therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Allosteric Regulation
  • Allosteric Site*
  • Animals
  • Disease / genetics*
  • Drug Discovery*
  • Drug Therapy
  • Enzymes
  • Humans
  • Models, Molecular
  • Protein Conformation*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Signal Transduction
  • Thermodynamics


  • Enzymes
  • Protein Kinase Inhibitors
  • Protein Kinases