The binding affinity of a protein-protein complex can be significantly affected by varying pH levels in the surrounding environment. This is because the pH level influences the ionization state of amino acid side chains, which in turn affects the overall charge, conformation, and stability of the proteins involved in the complex.At different pH levels, the ionizable groups on the amino acid side chains can either gain or lose protons H+ ions , leading to changes in the net charge of the protein. This can impact the electrostatic interactions between the proteins, as well as the hydrogen bonding and van der Waals forces that contribute to the stability of the protein-protein complex.For example, if the pH is lower than the pKa of an acidic amino acid side chain e.g., aspartic acid or glutamic acid , the side chain will be protonated and carry a negative charge. Conversely, if the pH is higher than the pKa of a basic amino acid side chain e.g., lysine, arginine, or histidine , the side chain will be deprotonated and carry a positive charge. These changes in charge can either promote or disrupt the binding of the protein-protein complex, depending on the specific interactions involved.Additionally, changes in pH can also lead to changes in protein conformation, as the ionization state of amino acid side chains can affect the overall folding and stability of the protein structure. This can further impact the binding affinity of the protein-protein complex, as the binding interface may be altered or even become inaccessible due to conformational changes.In summary, the binding affinity of a protein-protein complex can change with varying pH levels in the surrounding environment, as the ionization state of amino acid side chains affects the overall charge, conformation, and stability of the proteins involved. Understanding these effects is crucial for studying protein-protein interactions and for designing effective drugs and therapies that target specific protein complexes.