sentences:  In enzyme-catalyzed reactions, the overall activation energy of the reaction is lowered when an enzyme stabilizes a high energy transition state intermediate.Transition state analogs mimic this high energy intermediate but do not undergo a catalyzed chemical reaction and can therefore bind much stronger to an enzyme than simple substrate or product analogs.To design a transition state analogue, the pivotal step is the determination of transition state structure of substrate on the specific enzyme of interest with experimental method, for example, kinetic isotope effect.