Free Energy Decomposition Analysis Based on the Fragment Molecular Orbital Method.

A decomposition of the free energy is developed in the many-body expansion framework of the fragment molecular orbital (FMO) method combined with umbrella sampling molecular dynamics (MD). In FMO/MD simulations, performed with density-functional tight-binding and periodic boundary conditions, all atoms are treated quantum mechanically. The free energy is computed and decomposed for a series of S N 2 Menshutkin reactions in water. The barrier lowering by the solvent is attributed to the competition between the solvent polarization and the solute-solvent interactions including charge transfer.