Perspective: Free Energies and Phase Equilibria

Abstract

Analysis of the free energy is required to understand and predict the equilibrium behavior of thermodynamic systems, which is to say, systems in which temperature has some influence on the equilibrium condition. In practice, all processes in the world around us proceed at a finite temperature, so any application of molecular simulation that aims to evaluate the equilibrium behavior must consider the free energy. There are many such phenomena to which simulation has been applied for this purpose. Examples include chemical-reaction equilibrium, protein-ligand affinity, solubility, melting and boiling. Some of these are examples of phase equilibria, which are an especially important and practical class of thermodynamic phenomena. Phase transformations are characterized by some macroscopically observable change signifying a wholesale rearrangement or restructuring occurring at the molecular level. Typically this change occurs at a specific value of some thermodynamic variable such as the temperature or pressure. At the exact point where the transition occurs, both phases are equally stable — have equal free energy — and we find a condition of phase equilibrium or coexistence [1].