Cavitation Free Energy for Organic Molecules Having Various Sizes and Shapes

Abstract

Cavitation free energy DeltaG(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 A; spherical cavities with radii 3-6 A are also studied. The interaction between water molecules is described by the four-site nonpolarizable TIP4P 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 DeltaG(cav)V = XiV, where V is the cavity volume. This relation works fairly well until the cavity size becomes very large (the effective radius larger than 7 A). 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.