In addition to the large changes of the entropic reservoirs, small fluctuations within folded domains can contribute significantly to spatial entropic redistribution. The interplay between backbone and side chain in entropic spatial redistribution plays out in the relationship of peptide binding in PDZ domains. The third PDZ domain from PSD-95/SAP90 (PDZ3) shows a connection between a non-essential distal alpha helix and binding affinity. Truncation of alpha helix 3 (α3) reduces peptide binding affinity by 21-fold, even though it is over 6 Å away from the binding site. The lack of change in chemical shifts show this change is not due to a major structural perturbation change. Rather, the change is in the dynamics of the unbound state. In the wildtype protein, the side chains are much more rigid relative to the truncated variant. In the peptide bound state, both wildtype and the truncated variant have similar side chain dynamics. The change in binding affinity therefore results in the increased entropic penalty in the receptor. In this context, the α3 truncation is artificial, but it is a site where other domains are commonly linked to PDZ domains and may highlight a mechanism of inter-domain allosteric communication . This type of interaction is reminiscent of the "entropic reservoirs" discussed above; however, in this case the dominant entropic contribution is on the side chain dynamics of the folded domain, not on the backbone of the terminal segment. The dominance of side chain dynamics in dictating the entropic contributions also played out in a study in the homologous second PDZ domain of human tyrosine phosphatase 1E. This PDZ domain demonstrates clear spatial redistribution: side chains around the binding site lose entropy while specific distal residues increase entropy . As in the PDZ3 example, there is no evidence from chemical shifts that suggests a major conformational change. This result suggests that sub-angstrom changes in positions can be amplified non-linearly to enable alternative conformations of side chains at neighboring residues, greatly contributing to the number of states the protein populates. This is a provocative mechanism for a protein to have evolved ways to 'transfer' areas of higher entropy (i.e., more dynamics) through creating new voids and changes in rotamer states .