Abstract
Using the path integral formalism or the FeynmanβHibbs approach, various expressions for the free energy of quantization for a molecular system in the condensed phase can be derived. These lead to alternative methods to directly compute quantization free energies from molecular dynamics computer simulations, which were investigated with an eye to their practical use. For a test system of liquid neon, two methods are shown to be most efficient for a direct evaluation of the excess free energy of quantization. One of them makes use of path integral simulations in combination with a singleβstep free energy perturbation approach and was previously reported in the literature. The other method employs a FeynmanβHibbs effective Hamiltonian together with the thermodynamic integration formalism. However, both methods are found to give less accurate results for the excess free energy of quantization than the estimate obtained from explicit path integral calculations on the excess free energy of the neon liquid in the classical and quantum mechanical limit. Suggestions are made to make both methods more accurate. Β© 2008 Wiley Periodicals, Inc. J Comput Chem 2009