Where p𝐾 𝑎 𝑖 𝑤 refers to the p𝐾 𝑎 𝑖 𝑤 of the ith residue in water; 𝑞 𝑖 ̅ refers to the charge of the residue in its ionized form (+1 for cation, -1 for anion); ∆∆𝐺 𝑠𝑒𝑙𝑓,𝑖 𝑤→𝑝 represents the solvation free energy change by moving the charged form of the i th amino acid residue from water to its position in the protein when all other amino acids are neutral. This free energy change was calculated by the PDLD method. The second term in Eqn. ( ) can be obtained by Eqn. ( ):