 
Summary: Accurate Transferable Model for Water, nOctanol, and nHexadecane Solvation Free
Energies
A. J. Bordner, C. N. Cavasotto, and R. A. Abagyan*
The Scripps Research Institute, 10550 North Torrey Pines Road, Mail TPC28, 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 solventaccessible surface area. The model's parameters have been optimized using sets of
410, 382, and 2116 molecules for gaswater, gashexadecane, and wateroctanol 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 rootmeansquare error for gaswater, gashexadecane, 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 realtime calculations of the ADME properties of molecules in virtual
ligand screening libraries.
1. Introduction
The value of the free energy to transfer a solute from vapor
phase into a solvent is important for understanding a wide range
