A slightly different approach was used by one participant (0wfzo) where QM calculations of the free energy of deprotonation and thermodynamic integration, an MM method, were combined to calculate the difference of the solvation free energies between the acid and its conjugate base . This approach yielded an average level of performance, with an RMSE of 2.89 for the macroscopic acidity constants calculated from the submitted microscopic acidity constants, excluding two compounds (SM14 and SM18) from the analysis as they exhibited multiple pK a values too close to each other.