Protein ligand interactions and changes in conformational entropy a comparative study of QENS and NMR

Protein-ligand interactions and molecular fluctuations play an important role for the biological function of proteins. Molecular recognition by proteins is central to complex biochemistry. The thermodynamic origins of affinity remain somewhat obscure. Traditionally, high-resolution structures provided by crystallography provide deep insight into the enthalpic contributions to the free energy of binding. In contrast, the contribution of conformational entropy is much less understood. Furthermore, while the general contributions of non-specific interactions of solvent water with the protein surface are well understood, the detailed nature and role of protein hydration also remains obscure. The project proposed here will shed new light on both of these important topics in protein biochemistry and biophysics. The synergistic application of QENS and NMR methods will provide a unique insight into the role of conformational entropy and hydration to the thermodynamics of molecular recognition by proteins. To the best of our knowledge, no quantitative or qualitative comparison between NMR and QENS has been made. We expect that a quantitative comparison of the results obtained from these two methods will lead to an increased understanding of the contributions to the whole system entropy during protein ligand interactions.