Recently, the combination of state-of-the-art molecular mechanical force fields with continuum solvation models enables us to make relatively accurate predictions of both structures and free energies for macromolecules from molecular dynamics trajectories. The first part of this review is focused on the history and basic theory of free energy calculations based on physically effective energy functions. The second part illustrates the applications of free energy calculations on many biological systems, including proteins, DNA,RNA, protein-ligand, protein-protein, protein-nucleic acid complexes, etc. Finally, the prospective and possible strategies to improve the techniques of MM-PBSA and MM-GBSA is discussed.
Keywords: Molecular mechanics, continuum solvation model, MM-PBSA, MM-GBSA, Free energy, binding free energy