Biophysical Methods for Identifying Fragment-Based Inhibitors of Protein-Protein Interactions

  • Samuel J. Pfaff
  • Michael S. Chimenti
  • Mark J. S. Kelly
  • Michelle R. ArkinEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1278)


Fragment-based lead discovery complements high-throughput screening and computer-aided drug design for the discovery of small-molecule inhibitors of protein-protein interactions. Fragments are molecules with molecular masses ca 280 Da or smaller, and are generally screened using structural or biophysical approaches. Several methods of fragment-based screening are feasible for any soluble protein that can be expressed and purified; specific techniques also have size limitations and/or require multiple milligrams of protein. This chapter describes some of the most common fragment-discovery methods, including surface plasmon resonance, nuclear magnetic resonance, differential scanning fluorimetry, and X-ray crystallography.

Key words

Fragment Ligand Discovery Biophysics SPR NMR DSF Crystallography Protein-protein Interaction 


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Samuel J. Pfaff
    • 1
    • 2
  • Michael S. Chimenti
    • 2
  • Mark J. S. Kelly
    • 2
  • Michelle R. Arkin
    • 1
    • 2
    • 3
    Email author
  1. 1.Small Molecule Discovery CenterUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Department of Pharmaceutical ChemistryUniversity of California San FranciscoSan FranciscoUSA
  3. 3.UCSFSan FranciscoUSA

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