Terahertz calorimetry spotlights the role of water in biological processes.

Terahertz (THz) calorimetry is a framework that allows for the deduction and quantification of changes in solvation entropy and enthalpy associated with biological processes in real-time. Fundamental biological processes are inherently non-equilibrium, and a small imbalance in free energy can trigger protein condensation or folding. Although biophysical techniques typically focus mainly on structural characterization, water is often ignored. Being a generic solvent, the intermolecular protein-water interactions act as a strong competitor for intramolecular protein-protein interactions, leading to a delicate balance between functional structure formation and complete solvation. Characteristics for biological processes are large, but competing enthalpic and entropic solvation contributions to the total Gibbs free energy lead to subtle energy differences of only a few kJ mol^-1 that are capable of dictating biological functions. THz calorimetry spotlights these intermolecular coupled protein-water interactions. With experimental advances in THz technology, a new frequency window has opened, which is ideally suited to probe these low-frequency intermolecular interactions. The future impact of these studies is based on the belief that the observed changes in solvation entropy and enthalpy are not secondary effects but dictate biological function.