HTS reporter displacement assay for fragment screening and fragment evolution toward leads with optimized binding kinetics, binding selectivity, and thermodynamic signature

Methods Enzymol. 2011;493:299-320. doi: 10.1016/B978-0-12-381274-2.00012-1.

Abstract

Parameters such as residence time, kinetic selectivity, and thermodynamic signature are more and more under debate as optimization objectives within fragment-based lead discovery. However, broad implementation of these parameters is hampered by the lack of technologies that give rapid access to binding kinetics and thermodynamic information for large amounts of compound-target interactions. Here, the authors describe a technology--the reporter displacement assay--that is capable of opening this bottleneck and of supporting data-driven design of lead compounds with tailor-made residence time, kinetic selectivity, and thermodynamic signature.

MeSH terms

  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Kinetics
  • Mitogen-Activated Protein Kinase 14 / chemistry
  • Protein Binding*
  • Thermodynamics*

Substances

  • Mitogen-Activated Protein Kinase 14