Methods for the elucidation of protein-small molecule interactions

Chem Biol. 2013 May 23;20(5):667-73. doi: 10.1016/j.chembiol.2013.04.008.


Understanding the interactions between small molecules and proteins can be approached from different perspectives and is important for the advancement of basic science and drug development. Chemists often use bioactive small molecules, such as natural products or synthetic compounds, as probes to identify therapeutically relevant protein targets. Biochemists and biologists often begin with a specific protein and seek to identify the endogenous metabolites that bind to it. These interests have led to the development of methodology that relies heavily on synthetic and analytical chemistry to identify protein-small molecule and protein-metabolite interactions. Here, we survey these strategies, highlighting key findings, to demonstrate the value of these approaches in answering important chemical and biological questions.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery / methods*
  • Humans
  • Protein Binding
  • Proteins / metabolism*
  • Proteomics / methods*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism*
  • Small Molecule Libraries / pharmacology*


  • Proteins
  • Small Molecule Libraries