Among the physics-based models, the most straightforward approach involved calculation of the acidity constants without any empirical corrections, including the experimental value for the free energy of solvation of the proton . One group applied different calculation schemes to the compounds of the SAMPL6 challenge that differed in the use of gas phase and/or solution phase geometries as well as additional high-level single point gas phase calculations . While the results achieved by this method were quite promising, with an initial RMSE of 1.77 pK a units (ryzue) that could be improved to 1.40 by including a standard state correction and a different value for the free energy of the proton, the authors also showed the effectiveness of a simple linear regression scheme to correct the raw acidity constants. In this case the RMSE of the best-performing model decreased further from 1.40 to 0.73 pK a units after regression. This type of empirical correction was used by most QM-based approaches, including the best-performing method of the SAMPL6 challenge , improving some systematic deficiencies of the QM level of theory and basis sets and accounting for the proton's solvation free energy. The best-performing QM+LEC method, xvxzd, achieved an RMSE of 0.68 pK a units during the challenge using the COSMO-RS solvation model. This also made it the best-performing model overall, with two other methods using the same solvation model only slightly worse (yqkga and 8xt50, with RMSEs of 1.01 and 1.07 pK a units, respectively ).