Figure 12. Inaccuracy of pK_a prediction (± 1 unit) affects the the accuracy of MPSC and overall protein-ligand binding free energy calculations to varying degrees based on aqueous pK_a and relative binding affinity of individual protonation states $\Delta \Delta G=\Delta G_{bind}^C-\Delta G_{bind}^N)$.

All calculations are made for 25°C, and a ligand with a single basic titratable group. A, C, E, and G show MPSC (ΔG_corr) calculated with true vs. inaccurate pK_a. B, D, F, and H show the comparison of the absolute error to ΔG_bind caused by ignoring the MPSC completely (solid lines) vs. calculating MPSC based in inaccurate pK_a value (dashed lines). These plots provide guidance on when it is beneficial to include MPSC correction based on pK_a error, pH - pK_a, and ΔΔG.