We benchmarked the effect of different water models based on: a) Molecular Dynamics Simulations to study the structural effects and b) QM/MM calculations to study the effect on reactivity of Compound I (Cpd I) for three CYP450 members. The structural effects were probed using RMSD, RMSF, SASA, dipole moment, etc., while reactivity patterns were studied by the hybrid QM/MM calculations for the structure generated by three solvent models. The performance of different water models were ranked on the qualitative comparison depending on above parameters. In CYP450 chemistry, it is well established that the 'water occupancies' close to the heme site is crucial for the catalytic activity of the P450 enzymes. In fact, it is well known that destroying the water channel through the acid-alcohol pairs (for example Glu267-Thr268 in P450BM3) can inhibit the enzyme function. Therefore, we have used the population of water molecules close to the heme site as our standard parameter to measure the relative performance of each water model. In this way-a simulated system with more ordered and populated water molecules has been ranked better and vice versa.