It's important to note that this free energy change consider only electrostatic contributions, as other effects are accounted for within the intrinsic pKa values included in the initial summation. The 𝑞 𝑖 𝑚 and 𝑞 𝑗 𝑚 term refer to the i th and j th charge in the m th charge configuration of the protein; 𝑟 𝑖𝑗 refers to the distance between the centers of the i th and j th residues; 𝜀 𝑖𝑗 is the effective dielectric constant defined as Eqn. (8):