Where p𝐾 𝑎 𝑖𝑛𝑡,𝑖 𝑝 refers to intrinsic p𝐾 𝑎 of the i th residue, while all the other residues are kept neutral; ∆p𝐾 𝑎 𝑖𝑛𝑡,𝑖 𝑐ℎ𝑎𝑟𝑔𝑒𝑠 refers to change of the i th residue due to the interaction with other ionizable residues. The intrinsic p𝐾 𝑎 of the i th residue can be represented as Eqn. ( ):