Conformational changes of molecules are crucial elements in many biochemical processes, and also in molecular recognition. Here, we present a novel exact mathematical equation for the binding free energy of a receptor-ligand pair. It shows that the energetic contribution due to conformational changes upon molecular recognition is defined by the so-called Kullback-Leibler (KL) divergence between the probability distributions of the conformational ensemble of the biomolecule in the bound and free states. We show that conformational changes always contribute positively to the change in free energy and therefore disfavor the association process. Using the example of ligands binding to a flexible cavity of T4 lysozyme, we illustrate that, due to enthalpy-entropy compensation, the conformational entropy is a misleading quantity for assessing the conformational contribution to the binding free energy, in contrast to the KL divergence, which is the correct quantity to use in this context.