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Over the past 25 years, biophysical technologies such as X-ray crystallography, nuclear magnetic resonance spectroscopy, surface plasmon resonance spectroscopy and isothermal titration calorimetry have become key components of drug discovery platforms in many pharmaceutical companies and academic laboratories. There have been great improvements in the speed, sensitivity and range of possible measurements, providing high-resolution mechanistic, kinetic, thermodynamic and structural information on compound-target interactions. This Review provides a framework to understand this evolution by describing the key biophysical methods, the information they can provide and the ways in which they can be applied at different stages of the drug discovery process. We also discuss the challenges for current technologies and future opportunities to use biophysical methods to solve drug discovery problems.

The 4-hydroxyalk-2-enals are established products of lipid peroxidation that are conjugated with intracellular glutathione. Cytosolic glutathione transferases from rat liver were shown to give high specific activities with 4-hydroxynonenal and 4-hydroxydecenal. The isoenzyme giving the highest specific activity was glutathione transferase 4-4. The rate of the spontaneous conjugation reaction is negligible in comparison with the rate calculated for the cellular concentration of the glutathione transferases. It is proposed that a major biological function of the glutathione transferases is to protect the cell against products of oxidative metabolism, such as epoxides, organic hydroperoxides, and 4-hydroxyalkenals.