pH dependence of antibody/lysozyme complexation.

Association between proteins often depends on the pH and ionic strength conditions of the medium in which it takes place. This is especially true in complexation involving titratable residues at the complex interface. Continuum electrostatics methods were used to calculate the pH-dependent energetics of association of hen egg lysozyme with two closely related monoclonal antibodies raised against it and the association of these antibodies against an avian species variant. A detailed analysis of the energetic contributions reveals that even though the hallmark of association in the two complexes is the presence of conserved charged-residue interactions, the environment of these interactions significantly influences the titration behavior and concomitantly the energetics. The contributing factors include minor structural rearrangements, buried interfacial area, dielectric environment of the key titratable residues, and geometry of the residue dispositions. Modeled structures of several mutant complexes were also studied so as to further delineate the contribution of individual factors to the titration behavior.