Changes in pH can significantly affect the stability of protein-protein interactions and complexes. This is because the pH influences the ionization state of amino acid side chains, which in turn affects the overall charge distribution, folding, and stability of the protein. The stability of protein-protein interactions is determined by various factors, including electrostatic interactions, hydrogen bonding, hydrophobic interactions, and van der Waals forces. Changes in pH can disrupt these interactions, leading to altered protein conformations and reduced stability of protein complexes.1. Electrostatic interactions: Amino acid side chains can carry positive, negative, or neutral charges depending on their ionization state. At a specific pH, known as the isoelectric point pI , a protein will have a net charge of zero. When the pH is above or below the pI, the protein will have a net positive or negative charge, respectively. Changes in pH can alter the ionization state of amino acids, leading to changes in the electrostatic interactions between proteins. This can result in the disruption of protein-protein interactions and destabilization of protein complexes.Experimental evidence: In a study by Goh et al. 2004 , the effect of pH on the stability of the protein-protein interaction between barnase and barstar was investigated. The authors found that the binding affinity between the two proteins decreased as the pH was increased from 5.0 to 9.0, indicating that changes in pH can affect the stability of protein-protein interactions.2. Hydrogen bonding: Hydrogen bonds are essential for maintaining the secondary and tertiary structures of proteins. Changes in pH can alter the ionization state of amino acids, which can disrupt hydrogen bonding networks and lead to changes in protein conformation and stability.Experimental evidence: In a study by Schreiber and Fersht 1993 , the authors investigated the effect of pH on the stability of the protein-protein interaction between the enzyme subtilisin and its inhibitor, eglin c. They found that the binding affinity between the two proteins decreased as the pH was increased from 5.0 to 9.0, indicating that changes in pH can affect the stability of protein-protein interactions.3. Hydrophobic interactions: Hydrophobic interactions are crucial for maintaining the stability of protein-protein interactions and complexes. Changes in pH can alter the ionization state of amino acids, which can affect the hydrophobicity of protein surfaces and disrupt hydrophobic interactions.Experimental evidence: In a study by Kiefhaber et al. 1995 , the authors investigated the effect of pH on the stability of the protein-protein interaction between the enzyme ribonuclease A and its inhibitor, ribonuclease inhibitor. They found that the binding affinity between the two proteins decreased as the pH was increased from 5.0 to 9.0, indicating that changes in pH can affect the stability of protein-protein interactions.4. Van der Waals forces: Van der Waals forces contribute to the stability of protein-protein interactions and complexes. Changes in pH can alter the ionization state of amino acids, which can affect the distance between atoms and disrupt van der Waals forces.Experimental evidence: In a study by Schreiber and Fersht 1996 , the authors investigated the effect of pH on the stability of the protein-protein interaction between the enzyme subtilisin and its inhibitor, eglin c. They found that the binding affinity between the two proteins decreased as the pH was increased from 5.0 to 9.0, indicating that changes in pH can affect the stability of protein-protein interactions.In conclusion, changes in pH can significantly affect the stability of protein-protein interactions and complexes by altering the ionization state of amino acids and disrupting various forces that contribute to protein stability. Experimental evidence from various studies supports this notion, demonstrating the importance of maintaining optimal pH conditions for protein function and stability.