Solvation Model Based on Weighted Solvent Accessible Surface Area

We have developed a fast procedure to predict solvation free energies for both organic and biological molecules. This solvation model is based on weighted solvent accessible surface area (WSAS). Least-squares fittings have been applied to optimize the weights of SAS for different atom types in order to reproduce the experimental solvation free energies. Good agreement with experimental results has been obtained. For the 184-molecule set (model I), for which there are experimental solvation free energies in 1-octanol, we have achieved an average error of 0.36 kcal/mol, better than that of the SM5.42R universal solvation model1 by Li et al. For the 245-molecule set (model II) that has experimental aqueous solvation free energies, our WSAS model achieves an average error of 0.48 kcal/mol, marginally larger than that of Li's model (0.46 kcal/mol). We have used a 401-molecule set, the largest training set (model IV) that we know of solvation model development, to derive the SAS weights in order to reproduce th...