The success rate for protein- or RNA/DNA-ligand co-crystallization can be significantly improved by performing preliminary biophysical analyses. Among suitable biophysical approaches, isothermal titration calorimetry (ITC) is certainly a method of choice. 

ITC can be used in a wide range of experimental conditions to monitor in real time the formation of the RNA/DNA- or protein-ligand complex, with the advantage of providing in addition the complete binding profile of the interaction. Following the ITC experiment, the complex is ready to be concentrated for crystallization trials. 

Here we describe how ITC can be used as a tool for monitoring complex formation, followed by co-crystallization.