Comparative analysis of binding affinities between styrene and mammalian CYP2E1 by bioinformatics approaches.

Cytochrome P450 2E1 (CYP2E1) is a cytochrome P450 enzyme involved in styrene metabolism. This study compared the binding affinities between styrene and 11 mammalian CYP2E1 systems using bioinformatics methods. Firstly, amino acid sequences of CYP2E1s were obtained from the Swiss-Prot database. Then, taking the crystal structure of human CYP2E1 as a template, 3D models of the CYP2E1s of other mammals were constructed using the SWISS-MODEL program. Finally, the generated homology models were applied to calculate their docking capacities against styrene and polystyrene using the Surflex-Dock program, which could automatically dock ligands into a receptor's ligand binding site using a protomol based approach and assess the affinity by an empirically derived scoring function. Docking experiments showed that the studied mammalian CYP2E1s had high binding affinities with styrene. For polystyrene, the dimmer of styrene has high binding affinities with CYP2E1s, however, trimer and other high polymers were found hard to be docked into the CYP2E1s. The results of this study indicated that bioinformatics approaches might be useful tools to predict styrene and polystyrene affinities with mammalian CYP2E1s.