Biophysical Screening for Identifying Pharmacological Chaperones and Inhibitors Against Conformational and Infectious Diseases

Curr Drug Targets. 2016;17(13):1492-505. doi: 10.2174/1389450117666160201110449.


Experimental and computational screenings are currently widespread tools for identifying either potential ligands for a given target or potential targets for a given chemical compound. In particular, ligand-induced stabilization against thermal denaturation (or thermal shift assay) is an easy and convenient experimental procedure for finding compounds able to control the activity of a protein target (e.g., allosteric or competitive inhibitors interfering with its activity, allosteric activators enhancing its activity, or pharmacological chaperones avoiding aggregation, unfolding or degradation). Despite its simplicity the thermal shift assay does not lack some important drawbacks. Here we describe this methodology, its application to structured and unstructured protein targets, and we discuss successful cases of identification of bioactive compounds for conformational disorders associated to loss of function (phenylketonuria) and infectious diseases (gastric ulcer and hepatitis C).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Communicable Diseases / drug therapy
  • Communicable Diseases / physiopathology
  • Drug Design*
  • Humans
  • Ligands
  • Molecular Chaperones / pharmacology
  • Molecular Targeted Therapy*
  • Phenylketonurias / drug therapy
  • Phenylketonurias / physiopathology
  • Protein Conformation
  • Proteins / chemistry
  • Proteins / metabolism*


  • Ligands
  • Molecular Chaperones
  • Proteins