where v denotes vacuum and s denotes solvent. The average over v is evaluated by generating vacuum ensembles and computing the average of the exponential term in Equation . The solvent energy U s is evaluated using the improved Generalized Born model (GB-Neck2). GAFF and (GB-Neck2) have been experimentally validated for predicting free energies of solvation . A prediction of very high solvation energy can be due to both the molecule being not soluble (small overlap between vacuum and solvent ensemble) or that an ensemble that we generated (but not the ground-true vacuum ensemble) has low overlap. To be certain to have some statistical significance in our estimates we set a threshold of 100 effective samples to rely on the predicted free energy. This only discards 3% of the molecules.