Most thermodynamic measurements of binding reactions rely on the validity of the law of mass action and the assumption of a dilute solution. Yet, important biological systems such as allosteric ligand-receptor binding, macromolecular crowding, or misfolded molecules may not fulfill these assumptions and may require a particular reaction model. Today in an article published in Science by a team of the University of Barcelona, researchers have determined thermodynamic properties in biomolecular complex systems such as binding energies, chemical selectivity, and allostery of nucleic acids and peptides in a model-independent way.