Here the tight binding of syringol may inhibit further oxidation, and therefore, no activity is observed for S-unit in the WT P450GcoA enzyme which is similar to mechanism-based inhibition already been reported for cytochrome P450. To further validate this hypothesis, we performed a separate MD simulation of central intermediate 3MC in the resting state of the WT CYP450GcoA. As per our expectations, the intermediate 3MC was very stable in the resting state of the enzyme (see Figure ) and doesn't exhibit mobility, and hence would account for the inhibition of the second oxidation.