Thermodynamics of stacking interactions in proteins

This contribution is aimed at assessing the current knowledge of stacking interactions in proteins focusing on the thermodynamic origin of their strength. First, the energetic nature of p­p interactions is critically discussed by using recent accurate quantum chemical calculations. Then, the intimate relation between energetics and thermodynamics is analyzed via a survey on the last decade computer simulations and experimental data involving interactions of aromatic side chains in solution. The thermodynamics of stacking in protein is further assessed by reviewing studies based on a knowledge-based approach on updated databases of experimental protein structures. Finally the contribution selectively includes some recent authoritative progresses that highlights the paramount importance of stacking in the stabilization and destabilization of protein tertiary structures.