Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.

Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the ligand-binding site. The specificity of a protein’s ligand-binding site is determined by the arrangement of its amino acid chain which gives the area its shape and chemical reactivity. Hence, a ligand-binding site provides a complementary shape to its ligand and keeps the ligand in place via chemical interactions. These chemical interactions are often noncovalent; however, since these interactions are reversible and weak, many of these interactions need to occur simultaneously to hold the protein and the ligand together.

Research that elucidates interaction mechanisms at ligand binding sites generally involves in silico modeling and in vitro approaches. In silico modeling uses computers to compare previously known protein structures and evolutionary data to make predictions to determine the optimal binding shape and energy state of the protein-ligand complex. In vitro approaches compliment in silico predictions by providing evidence for ligand binding through binding and kinetic assays in the laboratory. Ligand binding research is important for understanding the functions of proteins and how they perform specific cellular processes in both healthy, as well as in diseased conditions. For instance, certain genetic conditions and cancers can alter the sequence of a protein, ultimately affecting its ability to bind a ligand. In addition, this research also allows scientists to design drugs with specific interactions and minimal side effects by targeting the ligand-binding site of an implicated protein.