So far, using MD simulation of the Michaelis Complex and TSA, we have seen that the local electric field produced by enzyme provides an entropic favor in transition state. However, we complemented our study with QM/MM calculations and a gas-phase Density Functional Calculations to elaborate the role of electrostatics on the activation energy for chorismate to prephenate. The gas-phase density functional calculations show that conversion of chorismate to prephenate is an energetically demanding process and the energy barrier for this process (in absence of enzymatic system) is 32.90 kcal/mol (Figure ). Interestingly, when we included the enzyme environment using QM/MM calculations the barrier of the same reaction decreased by a significant amount (see Figure for QM/MM reaction profile). The QM/MM calculation was started by considering a representative snapshot from the MD simulations and a subsequent optimization of the Michaelis Complex. A relaxed potential energy surface (PES) scanning was performed for the conversion of chorismate to prephenate. The energy profile shows a feasible reaction with a TS barrier of 15.1 kcal/mol for this transformation when it occurs in the enzymatic environment. In addition, the product prephenate is more exothermic relative to the gas-phase reaction.