Several past challenges focused on solvation modeling in order to help address this accuracy-limiting component of proteinligand modeling. The SAMPL0 through SAMPL4 challenges included hydration free energy prediction, followed by cyclohexanewater distribution coefficient prediction in SAMPL5, and octanol-water distribution coefficient prediction in SAMPL6. Large errors were observed in the SAMPL5 cyclohexane-water log D prediction challenge due to tautomers and protonation states not being taken into account or adequately handled. Many participants reported log P predictions in place of log D predictions, in part because the different ionization states of the molecules were thought not to be particularly relevant in the challenge, but this proved not to be the case. Methods that treated multiple protonation and tautomeric states and incorporated pK a corrections (which relies on accurate pK a prediction) in their predictions performed better .