Despite the apparent energetic importance of conformational entropy, the ability to probe it experimentally is underdeveloped. Currently, the best experimental support comes from NMR relaxation techniques. By probing methyl or amide groups, NMR relaxation techniques obtain a sitespecific measurement of the amount of disorder on the pico-nanosecond timescale, called an order parameter . Changes in the average side chain order parameter for methyl-containing residues (like leucine) across a protein have been correlated with calorimetric measurements of conformational entropy . Excitingly, these experiments reveal a great diversity of behaviors across systems: some binding events are entropically driven due to increased side chain disorder whereas others are strongly entropically disfavored. Additionally, some side chains exhibit increased disorder even when the overall trend is towards unfavorable conformational entropy (and vice versa). Furthermore, different ligands bound to the same receptor can have drastically different impacts on conformational entropy . While NMR order parameters provide the extent of the disorder, many equivalent side chain conformational ensembles can produce a given order parameter value, as seen in the packing void example (Figure ,E) . This degeneracy makes it challenging to connect conformational entropy to structural models.