Performance of SM6, SM8, and SMD on the SAMPL1 Test Set for the Prediction of Small-Molecule Solvation Free Energies

Abstract

The SM6, SM8, and SMD quantum mechanical aqueous continuum solvation models are applied to predict free energies of aqueous solvation for 61 molecules in the SAMPL1 test set described elsewhere (Guthrie. J. Phys. Chem. B 2009, 113, 4501-4507). For direct comparison to other models, frozen geometries, provided by Guthrie, were used together with the M06-2X density functional and the 6-31G(d) basis set. For the bulk electrostatic component of the solvation free energy, SM6 and SM8 employ a generalized Born model that uses polarized discrete partial atomic charges to model the electron density, with these charges being calculated by the CM4 and CM4M class IV charge models, respectively; SMD uses the polarized continuous quantum mechanical charge density. If five sulfonylureas are removed from the SAMPL1 set, the root-mean-square deviations (RMSDs) of SM6, SM8, and SMD on the remaining 56 molecules are 2.4, 2.6, and 2.5 kcal mol(-1), respectively. The SM6, SM8, and SMD RMSDs on the five sulfonylureas are 14.2, 12.6, and 11.1 kcal mol(-1), respectively; however, we suggest that the uncertainty in the target solvation free energies for these molecules may be quite large.