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.