To begin, we perform a semi-empirical AM1 calculation for each microstate and then extract several properties. The first feature mirrors gas phase acidity by taking the difference in enthalpy between the protonated and deprotonated form of the molecule. For the protonated form of the molecule, the Mayer partial bond order is also calculated for the bond between the ionized atom and the hydrogen to be removed . AM1-BCC partial charges are calculated for atoms one and two bonds away from the ionized atom . Previous work established partial charges as a useful feature to predict pK a on molecules. These studies used molecule sets with all the same ionizable groups considering the charge on the deprotonated and surrounding atoms . In order to apply our model to all identified ionizable groups, we needed a more general approach. We decided to consider the partial charge of (1) the deprotonated atom and the average partial charge on atoms (2) one bond and (3) two bonds away from this atom, for both the protonated and deprotonated forms of the molecule (Figure ). This leads to six features based on the partial atomic charges. Since the AM1 calculations are performed in gas phase, the last two features attempt to capture the affect of solvation on the equilibrium. The difference in solvation free energy of the two forms of the molecule is estimated by a Poisson Boltzmann surface area calculation as implemented in OpenEye's Szybki toolkit . Lastly, the solvent accessible surface area around the deprotonated atom is determined with OpenEye's Spicoli Toolkit .