Ligand binding can also, counterintuitively, increase the conformational entropy of side chains . For example, a ligand binding at a different part of the active site may stabilize different residues in conformations that create a small void adjacent to the leucine. The void could permit populating an additional, third, leucine rotameric conformation compared to apo (Figure ) or increase the thermal fluctuations around the two already populated rotameric conformations (Figure ). Both of these scenarios increase conformational entropy and can, therefore, favor ligand binding.