Water is much more than a passive spectator during biological processes, such as enzyme-substrate binding, proteins folding. Solvation entropy and enthalpy changes actively contribute to shape the free energy landscape. Usually, the entropic and enthalpic solvation terms are large, but compensate each other with a subtle entropy/enthalpy balance, resulting in small free energy differences that can be tuned with small adjustment of e.g. temperature, concentration. Understanding such balance remained out-of-reach so far as it requires mapping the complex interplay of local hydrophobic and hydrophilic solvation contributions. 

I will present a novel approach, called THz-caloriemtry, to quantify the solvation entropy and enthalpy changes during biological processes directly from experimentally measured THz spectra.[1] The main advantages are two: (i) the THz spectra can be recorder as a function of time, with time resolutions down to ps, allowing to follow the free energy changes during chemical processes in real-time; (ii) we can dissect and interpret the thermodynamic quantities by deconvolving the THz spectra into local solvation contributions. I will illustrate the relevance of this approach to quantify and interpret solvation effects in biological processes with two applications.