title: Biophysical methods for identifying fragment-based inhibitors of protein-protein interactions.
abstract: 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.
authors: Small Molecule Discovery Center, University of California San Francisco, San Francisco, CA, USA.
authors: Samuel J
authors: SJ
authors: Pfaff
authors: Michael S
authors: MS
authors: Chimenti
authors: Mark J S
authors: MJ
authors: Kelly
authors: Michelle R
authors: MR
authors: Arkin
mesh_terms: D001703:Biophysics / Q000379:methods*; D017076:Computer-Aided Design; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D060066:Protein Interaction Maps / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D020349:Surface Plasmon Resonance
chemical_list: D054852:Small Molecule Libraries