Coulomb interactions closer than the cutoff distance were modified using the reaction field method and no periodic conditions were applied. A new fast optimizer to run on GPUs was programmed to ensure that energy minimization follows similar convergence criteria for all protein-ligand complexes (see Supporting Info). Example input files for OpenMM or AM-BER are provided in the Supporting Info. Before scoring, all explicit waters were stripped out of the structure leaving only the protein, ligand, and ions.