Chapter 8. Protein-ligand interactions

by József Kardos

Table of Contents

8.1. Biomolecular interactions
8.2. Reaction kinetics
8.3. Protein-ligand interactions
8.4. Relationship between the free enthalpy (Gibbs free energy) change and the equilibrium constant
8.5. Molecular forces stabilising ligand binding
8.6. Determination of the binding constant
8.7. Methods for the experimental determination of the binding constant
8.7.1. Surface plasmon resonance (SPR)
8.7.2. Isothermal titration calorimetry (ITC)
8.7.3. Fluorescence depolarisation to characterise protein-ligand binding interactions
8.8. Test questions and problems

8.1. Biomolecular interactions

All functions of living systems ranging from primitive bacteria to higher-order organisms, as well as their interactions with their environment, are realised through macromolecular interactions. These interactions might be simple or rather complex—with at least one of the partners being a biological macromolecule, usually a protein. In this chapter we briefly discuss the various types of interactions of proteins, their molecular background, theory and some practical applications.

Protein interactions can be classified into different groups regarding the molecular properties and functions of the interacting partners. (These groups are intertwined in several cases.) Some examples include:

  1. The interactions of proteins with other proteins, small molecules, carbohydrates, lipids or nucleic acids;

  2. Receptor-ligand interactions;

  3. Antigen-antibody interactions;

  4. Enzymatic interactions, enzyme-inhibitor interactions.

In the following, these reactions will be denoted as protein-ligand interactions. Such interactions often play key roles in the initiation of complex multi-step reactions. As an example, ligand binding—such as that of steroid hormones to their cytoplasmic or nuclear receptors or the binding of secreted peptide ligands to transmembrane receptors—might activate a receptor molecule, which induces a cellular response.