NMR relaxation studies of the role of conformational entropy in protein stability and ligand binding

Recent advances in the measurement and analysis of protein NMR relaxation d ata have made it possible to characterize the dynamical properties of many backbone and side chain groups. With certain caveats, changes in flexibilit y that occur upon ligand binding, mutation, or changes in sample conditions can be interpreted in terms of contributions to conformational entropy. Ba ckbone and side chain flexibility can either decrease or increase upon liga nd binding. Decreases are often associated with "enthalpy-entropy compensat ion" and "induced fit" binding, whereas increases in conformational entropy can contribute to stabilization of complexes. In certain cases, conformati onal entropy appears to play a role in cooperative binding and enzyme catal ysis. In addition, variations in conformational entropy and heat capacity m ay both be important in stabilizing the folded structures of proteins.