Summary: Accurate Transferable Model for Water, n-Octanol, and n-Hexadecane Solvation Free
A. J. Bordner, C. N. Cavasotto, and R. A. Abagyan*
The Scripps Research Institute, 10550 North Torrey Pines Road, Mail TPC-28, San Diego, California 92037
ReceiVed: July 3, 2002; In Final Form: August 13, 2002
We present a fast continuum method for the calculation of solvation free energies. It is based on a continuum
electrostatics model with MMFF94 atomic charges combined with a nonelectrostatic term, which is a linear
function of the solvent-accessible surface area. The model's parameters have been optimized using sets of
410, 382, and 2116 molecules for gas-water, gas-hexadecane, and water-octanol transfer, respectively.
These are the largest, most diverse sets of molecules used to date for a similar solvation model. The model's
predictive power was verified by using 90% of the molecule set for training and the remainder as a test set.
The average test set errors differed by only about 1% from the average training set error, thus demonstrating
the transferability of the parameters. The root-mean-square error for gas-water, gas-hexadecane, and water-
octanol transfer are 0.53, 0.38, and 0.58 log P units, respectively. Because the solvation calculation takes on
average only about 0.34 s per molecule on a 700 MHz Pentium CPU and contains atom types for essentially
all drug molecules, it is suitable for real-time calculations of the ADME properties of molecules in virtual
ligand screening libraries.
The value of the free energy to transfer a solute from vapor
phase into a solvent is important for understanding a wide range