Journal of Physical Chemistry B, Vol.111, No.49, 13748-13755, 2007
Cavitation free energy for organic molecules having various sizes and shapes
Cavitation free energy Delta G(cav) corresponding to the formation of an excluded volume cavity in water, is calculated for a large set of organic molecules employing the thermodynamic integration procedure, which is realized as the original two-step algorithm for growing the interaction potential between the hard cavity wall and the water molecules. A large variety of solute systems is considered. Their characteristic radii change in the range 3-7 angstrom; spherical cavities with radii 3-6 angstrom are also studied. The interaction between water molecules is described by the four-site nonpolarizable TIP41 model. The diversity of the trial molecular set is provided by using a specially formulated nonspherical criterion classifying the cavity shapes according to their deviation from a sphere. Molecular objects were partly taken from the data base NCI Diversity with the aid of this criterion. The so-computed free energies are approximated by the linear volume dependence Delta G(cav)(V) = xi V, where V is the cavity volume. This relation works fairly well until the cavity size becomes very large (the effective radius larger than 7 angstrom). The volume dependence valid for solutes of arbitrary shapes can be included in a calculation of the nonpolar free energy component as required in the implicit water model.