Enzymes are flexible structures that evolve during the catalytic cycle. To function, enzymes must be stable enough to retain their three-dimensional structure but flexible enough to permit the evolution of the protein among the different conformational states that are relevant at each step of the catalytic process. The participation of protein motions in the reaction progress is a well-established fact that has been invoked using different terminology: protein reorganization, coupled motions or promoting vibrations. However, the impact of protein motions on the rate constant of the chemical step remains as the subject of a long-standing debate between different battle fronts in the field. A fundamental question is if these motions can be described as equilibrium fluctuations, as assumed in Transition State Theory, or if their dynamics must be explicitly considered to explain some experimental observations such as the temperature dependence of Kinetic Isotope Effects or the consequences of distal point mutations on rate constants. The use of enzymes where some of the atom types (typically N, C and nonpolar H atoms) are substituted by heavier isotopes have opened a new perspective to analyze the role of protein motions, providing a meeting point between experimentalist and theoreticians. In principle, heavy enzymes differ from their light versions exclusively in their dynamics while the Potential Energy Surface remains unaltered. In this talk I will present the results of a cooperative work between experimental and theoretical groups to elucidate the role of protein dynamics in the chemical step of E. Coli DihydroFolate Reductase (DHFR) and other enzymes.