The importance of side chain entropy and the relevance of spatial redistribution to ligand binding extends beyond soluble proteins to membrane proteins. Many membrane proteins have high side chain conformational entropy in their apo state, which may offset the entropic penalty of sitting in the membrane . The modulation of these dynamics upon ligand binding can influence binding and allostery . For example, some GPCRs exhibit similar binding affinities for agonists and antagonists . Multiple studies have identified how subtle changes in side chain conformational dynamics in the presence of either agonists or antagonists can influence the relative stability of specific conformations compatible with distinct binding downstream partners . These results suggest a role for conformational entropy, located in specific distal regions of the protein, in controlling the free energy of binding and the output of allosteric signaling.