  Free energies of molecules can be calculated by quantum computations or by
normal mode classical calculations. However, the first can be computationally
impractical for large molecules and the second is based on the assumption of
harmonic dynamics. We present a novel, accurate and complete calculation of
molecular free energies in standard classical potentials. In this method we
transform the molecule by relaxing potential terms which depend on the
coordinates of a group of atoms in that molecule and calculate the free energy
difference associated with the transformation. Then, since the transformed
molecule can be treated as non interacting systems, the free energy associated
with these atoms is analytically or numerically calculated. This two-step
calculation can be applied to calculate free energies of molecules or free
energy difference between (possibly large) molecules in a general environment.
We suggest the potential application of free energy calculation of chemical
reactions in classical molecular simulations.
