The SAMPL7 pK a challenge participants were asked to predict relative free energies between microstates to determine the pK a of molecules. We define distinct protonation microstates as all possible tautomers of each ionization (charge) state. Participants could consider any of these microstates in their predictions, and had the option of submitting others. Participants were provided a reference microstate for each compound, and asked to predict transition free energies to all microstates they viewed as relevant, relative to this reference state.