Adding calorimetric data to decision making in lead discovery: a hot tip.
Recognition of the limitations of high-throughput screening approaches in the discovery of candidate drugs has reawakened interest in structure-based and other rational design methods. Here, we describe how isothermal titration calorimetry can be used to obtain thermodynamic data on the binding of compounds to protein targets. We propose that these data--particularly the change in enthalpy--could provide a valuable, complementary addition to established tools for selecting compounds in lead discovery and for aiding lead optimization.
Ladbury
John E
JE
University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jeladbury@mdanderson.org
Klebe
Gerhard
G
Freire
Ernesto
E
D002151:Calorimetry / Q000379:methods*; D003657:Decision Making; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004345:Drug Industry / Q000379:methods; D011485:Protein Binding; D013816:Thermodynamics