The binding affinity between two proteins plays a crucial role in determining the success rate of protein-protein interaction PPI inhibitors designed using molecular docking studies. Binding affinity is a measure of the strength of the interaction between two proteins, and it is usually represented as the dissociation constant Kd or the binding free energy G . A lower Kd or more negative G value indicates a stronger interaction between the proteins.In molecular docking studies, the goal is to identify small molecules inhibitors that can disrupt the protein-protein interaction by binding to one of the proteins involved in the interaction, thereby preventing the formation of the protein complex. The success of these inhibitors depends on their ability to compete with the native protein partner for binding to the target protein.The binding affinity between the two proteins in the PPI can affect the success rate of the designed inhibitors in several ways:1. High-affinity interactions: If the native protein-protein interaction has a high binding affinity low Kd or highly negative G , it may be more challenging to design inhibitors that can effectively compete with the native protein partner for binding to the target protein. In this case, the inhibitors need to have an even higher binding affinity for the target protein to successfully disrupt the PPI.2. Low-affinity interactions: If the native protein-protein interaction has a low binding affinity high Kd or less negative G , it may be easier to design inhibitors that can effectively compete with the native protein partner for binding to the target protein. In this case, the inhibitors may not need to have an extremely high binding affinity for the target protein to successfully disrupt the PPI.3. Specificity: The binding affinity between the two proteins can also affect the specificity of the designed inhibitors. If the native protein-protein interaction has a high binding affinity and the interaction interface is highly specific, it may be easier to design inhibitors that selectively target the PPI without affecting other unrelated protein interactions. On the other hand, if the native protein-protein interaction has a low binding affinity and the interaction interface is less specific, it may be more challenging to design inhibitors that selectively target the PPI without causing off-target effects.In summary, the binding affinity between two proteins in a PPI can significantly impact the success rate of protein-protein interaction inhibitors designed using molecular docking studies. High-affinity interactions may require more potent inhibitors to effectively disrupt the PPI, while low-affinity interactions may be easier to target. Additionally, the specificity of the interaction can also influence the success of the designed inhibitors.