**1. Introduction**

Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. Protein–ligand interactions play an important role in most biological processes, such as signal transduction, cell regulation, and immune response. Therefore, the study of protein–ligand interactions continues to be very important in life science fields. Since the recognition of their importance at the beginning of the 20th century, investigations into binding parameters have received significant attention, and understanding of these interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for protein–ligand recognition and binding also facilitates the discovery, design, and development of drugs.

Quantifying the binding of chemical entities to a protein is an important early screening step during drug discovery and is of fundamental interest for estimating safety margins during drug development. Current progress in experimental and computational methods for identifying and characterizing ligand binding sites on protein targets has provided biological insights that are significant for drug discovery. In addition, because the aim of rational drug design is to make use of knowledge of the structural data and protein–ligand binding mechanisms to optimize the process of finding new drugs, an in-depth understanding of the nature of molecular recognition/interactions is also of great importance. For a deeper understanding of the molecular recognition between a protein and its ligand, physicochemical mechanisms underlying the protein–ligand interaction, the binding kinetics, the basic thermodynamic concepts and relationships relevant to protein–ligand binding, and the driving forces/factors of binding and enthalpy–entropy compensation are investigated using experimental and theoretical methods and using various techniques such as isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and fluorescence, circular dichroism, and UV absorption spectroscopy.
