Abstract

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.

Author affiliations

1. John E. Ladbury is at the University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
2. Gerhard Klebe is at the Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 635032 Marburg, Germany.
3. Ernesto Freire is at the Department of Biology, Johns Hopkins University, 3400 North Charles Street 114 Biology East, Baltimore, Maryland 21218, USA.

Correspondence to: John E. Ladbury¹ Email: jeladbury@mdanderson.org

Published online 4 December 2009

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