title: Higher throughput calorimetry: opportunities, approaches and challenges.
abstract: Higher throughput thermodynamic measurements can provide value in structure-based drug discovery during fragment screening, hit validation, and lead optimization. Enthalpy can be used to detect and characterize ligand binding, and changes that affect the interaction of protein and ligand can sometimes be detected more readily from changes in the enthalpy of binding than from the corresponding free-energy changes or from protein-ligand structures. Newer, higher throughput calorimeters are being incorporated into the drug discovery process. Improvements in titration calorimeters come from extensions of a mature technology and face limitations in scaling. Conversely, array calorimetry, an emerging technology, shows promise for substantial improvements in throughput and material utilization, but improved sensitivity is needed.
authors.affiliation: Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CA 94304, USA. torres@parc.com
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Torres
authors.forename: Michael I
authors.initials: MI
authors.lastname: Recht
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Coyle
authors.forename: Richard H
authors.initials: RH
authors.lastname: Bruce
authors.forename: Glyn
authors.initials: G
authors.lastname: Williams
mesh_terms: D002151:Calorimetry / Q000295:instrumentation / Q000379:methods*; D055808:Drug Discovery; D057166:High-Throughput Screening Assays / Q000379:methods*; D015203:Reproducibility of Results; D013816:Thermodynamics