We chose to have participants report relative free energies of microstates for simplicity of analysis. Particularly, for each molecule, participants were asked to predict the relative free energy, including the proton free energy, between our selected neutral reference microstate and the rest of the enumerated microstates for that molecule at a reference pH of 0 (see Section 1.3 on approaches to calculating pK a ).This can also be thought of as a reaction free energy for the microstate transition where the reference state is the reactant and the other microstate the product (though a proton may also be a product, depending on the direction of the transition). As an example for one molecule, we asked for the reaction free energy (relative free energy) associated with each of the reactions as seen in Figure . This approach differs from that used in past pK a challenges, which typically focused on macroscopic pK a predictions. The shift, here, helps resolve several key problems: