Another ranked submission which performed well used MM/PBSA, and non-ranked variants of this explored variations based on both MM/PBSA and MM/GBSA. One variation assessed the charge model, and found that the RESP charge scheme led to improved performance compared to the AM1-BCC charge scheme (RESP/GAFF/MMPBSA vs AM1-BCC/GAFF/MMPBSA), as shown by RMS errors of 7.59 kcal/mol vs 10.96 kcal/mol. These methods predicted binding free energies to be too favorable, a common issue with such endpoint free energy methods, especially when entropy changes are neglected, as here. An additional variation assessed the difference between MM/PBSA and MM/GBSA by changing the solvent model; the use of PB solvation resulted in significantly lower RMS errors here (RESP/GAFF/MMPBSA vs RESP/GAFF/MMGBSA), though the correlation with the GB approach was modestly better. A further variation added an accounting for entropy via normal mode analysis (RESP/GAFF/MMPBSA/Nmode) while maintaining RESP charges and PB solvation. This improved typical errors, but hurt correlation and resulted in binding free energies often not being favorable enough. One other key difference between the ranked submission in this series, and many of the others was that it actually used an empirical correction to binding free energies. Particularly, RESP/GAFF/MMPBSA-Cor used a linear correction derived from an analysis of previous SAMPL challenges . Indeed, this correction led to much better agreement with experiments. With RMSE and ME values of 1.32 and 1.01 kcal/mol, the RESP/GAFF/MMPBSA-Cor performance was on par with alchemical AMOEBA results, and for some guests performed even slightly better. In terms of correlation, the ranked RESP/GAFF/MMPBSA-Cor was similar to that of RESP/GAFF/MMPBSA. However, such an approach could not be applied without prior binding studies for the specific system(s) of interest.