| Long-range intraprotein interactions in the native state give rise to many important protein behaviors. In an effort to understand such linkages, we have undertaken NMR studies of small, globular proteins that enable us to study the effects of mutation and ligand-binding on the structure and dynamics in these systems. Because proteins are highly dynamic molecules, the experimentally detected motions serve as excellent reporters of energy transmission through the network of interactions. Through these dissections we find that the impact of even conservative perturbations to a protein can propagate to distal regions of the structure. Such long-range "dynamic coupling" is found in PDZ domains, as well as in clear cases of globular proteins that exhibit no functional allostery. These findings have implications for understanding canonical allostery, protein stability, protein design, and drug design. |
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