Figure 3.

A thermodynamic cycle for calculating binding energy using the PDLD/S method. l and l′ represents the charged and uncharged forms of the ligand, respectively, while ℓ″ and represents the ligand being reduced to “nothing”. The inner binding cycle (b→c→d→a) corresponds in part to the cycle described in Ref²⁸. The electrostatic terms associated with b→c and d→a are evaluated by the external cycles in the figure (b→g→h→c and d→j→i→a) and are evaluated by using Eqs. 2 and 3 (in the text) with ε_in = 4. The free energy $\Delta G_{bind}^{l’}$ and the other contributions of $\Delta G_{bind}^{l’}$ are evaluated by Eq. 5 (in the text) using an approximation to the c→e→f→d cycle. For more details, see Ref²⁴, 25.