Conformational entropy in protein stability, molecular recognition and allosteric regulation

We have developed variety of NMR and analytical strategies to extract changes in conformational entropy that accompany the binding of a ligand by a protein. We have found that characterization of solution NMR relaxation in methyl-bearing amino acid side chains can be used as a reliable proxy for changes in this previously elusive thermodynamic quantity. Employing over two-dozen protein-ligand interactions, involving a range of ligand types, we have found that conformational entropy can strongly disfavor, strongly favor or sometimes not contribute to the free energy of binding.