Hydration Predictions in the SAMPL4 Event

Here we test a method, called Semi-Explicit Assembly (SEA), to computes the solvation free energies of molecules in water in the SAMPL4 blind test challenge. The blind aspect of this test is important, because this makes for stringent assessment of solvation free energy methods as general and automated processes. Our method, SEA, was developed with the intention of being as accurate as explicit solvent models, but much faster to compute. We find that the newest field variant of SEA performs as well as the earlier versions on this broad blind SAMPL4 test set. We find that both the past and present SEA models give solvation free energies that are as accurate as explicit solvent. Finally, using a new approach for force field parameter optimization using dielectric constants, we found improved predictions of solvation free energies for hydroxyl-containing compounds.