Modelling approaches and modern simulations to investigate the biomolecular structure and function rely on various methods, one among which is the choice of the water model. Water molecules play a crucial role in all sorts of chemistry. Cytochrome P450 (CYP450), in particular, water molecules are crucial for the formation of active oxidants which perform the oxidation and metabolism of several substrates. Computational chemistry tools such as MD simulations and QM/MM calculations, nowadays, have become complementary tools to study the structure and functions of CYP450 enzymes, and therefore, accurate modeling of water molecules is crucial. In the present study, we have highlighted the behavior of the three most widely used water models—TIP3P, SPC/E, and OPC for three different CYP450 enzymes—CYP450BM3, CYP450OleT, and CYP450BSβ during MD simulations and QM/MM calculations. We studied the various properties such as RMSD, RMSF, H-bond, water occupancy in the first solvation shell, and Hydrogen Atom Transfer (HAT) using QM/MM calculations and compared them for all the three water models. Our study shows that the stability of the enzyme structure is well maintained in all three water models. However, OPC water model performs well for the polar active sites, i.e., in CYP450OleT, CYP450BSβ while the TIP3P water model is superior for the hydrophobic site such as CYP450BM3.
Supporting material contains QM coordinated, RMSD and other relevant data for the manuscript.