Enzymes are well-defined chemical structures at the molecular level. They cannot perform their “catalytic fete” from a distance—enzymes must come in intimate contact with their substrates (reactants). The interaction of an enzyme (E) and its cognate substrate (S) begins the moment the two come together through diffusion. Specific interactions and binding result in the formation of the enzyme–substrate (ES) complex. All the transition state(s) and intermediate(s) are represented in this simplified version of the ES complex.