While there are examples of "fuzzy" ligand-protein binding events where both the protein and ligand adopt many conformations upon binding , most binding events involve a local reduction in conformational dynamics at the binding site . As in folding, this creates an entropic cost that the new attractive interactions between ligand and receptor must counter. Pre-paying this entropic cost with a ground state with a relatively less dynamic binding site is an attractive strategy, as stated above. However, such well-packed binding sites are at odds with the fact that most binding sites have large voids that can be filled by alternative conformations of binding site residues in the unbound form.