From here we will refer to ∆∆G s,p (A H → A -) as ∆∆G. Equation 3 implicitly contains two terms, which we here call ∆∆G env and ∆G titr , following the notation of Sharp and Honig . The first (∆∆G env ) represents the free energy of dissociating a proton within a protein relative to the solvent environment, which we represent by a capped peptide. It is assumed that the protein is fixed in some protonation state and, based on Tanford and Kirkwood, has often been taken to be the state in which all titratable sites in the protein are neutralized. Because these sites are fixed to some state, this free energy is pH-independent. The second free energy component (∆G titr ) reintroduces pH dependence by capturing how the free energy of dissociating the proton within the protein will be more or less favorable, depending on the states of the other protonatable sites.