Abstract
This Perspective reviews the use of Transition Path Sampling methods to study enzymatically catalyzed chemical reactions. First applied by our group to an enzymatic reaction over 15 years ago, the method has uncovered basic principles in enzymatic catalysis such as the protein promoting vibration, and it has also helped harmonize such ideas as electrostatic preorganization with dynamic views of enzyme function. It is now being used to help uncover principles of protein design necessary to artificial enzyme creation.