Optimization of the five GB cavity radii (carbon, nitrogen, oxygen, general hydrogen, and hydrogen bonded to nitrogen) led to a marked reduction in error for the training set (Figure , Table ) with the overall RMSE falling from 21.0 kcal/mol to 2.9 kcal/mol. Improvements were also seen for each separate host class, falling to 2.5 kcal/mol, 1.4 kcal/mol, and 4.4