Binding free energies Despite having far fewer numerical parameters, SMIRNOFF99Frosst does about as well as GAFF v1.7 and arguably better than GAFF v2.1 at replicating binding free energies measured by ITC or NMR. Thus, SMIRNOFF99Frosst yields an overall ΔG° RMSE from experiment of 0.9 [0.7, 1.1] kcal/mol across the 43 host-guest systems, compared to the statistically indistinguishable 0.9 [0.7, 1.1] kcal/mol for GAFF v1.7, and distinct from 1.7 [1.5, 1.9] kcal/mol for GAFF v2.1 (where the 95% confidence interval is written in brackets) as detailed in Figure ; Tables .