Accurate Transferable Model for Water, n-Octanol, and n-Hexadecane Solvation Free Energies

BORDNER, ANDREW J.; CAVASOTTO, CLAUDIO N.; ABAGYAN, RUBEN A.

JOURNAL OF PHYSICAL CHEMISTRY B - (Print)

AMER CHEMICAL SOC

Año: 2002 vol. 106 p. 11009 - 11015

1520-6106

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.