Cytochrome P450 enzymes (P450s) are among the most robust biological catalysts, playing indispensable roles across various organisms, including humans. However, experimental characterization of various short-lived intermediates and transition states of P450s is challenging, leaving the catalytic mechanism not yet entirely clear. Additionally, P450 inhibition is a significant public health concern due to its close relevance to adverse drug reactions arising from drug-drug interactions (DDIs). Understanding the molecular mechanisms of cytochrome P450s is therefore crucial, not only for academic interest but also for accurately predicting the DDI liabilities of drug candidates. To this end, we employ computational chemistry techniques to illuminate various facets of P450s. (1)      Enhua Zhang and Hajime Hirao, "Synergistic Charge Transfer Effect in Ferrous Heme–CO Bonding within Cytochrome P450", Molecules 2024, 29, 873. https://www.mdpi.com/1420-3049/29/4/873(2)      Dongxiao Yue and Hajime Hirao, "Mechanism of Selective Aromatic Hydroxylation in the Metabolic Transformation of Paclitaxel Catalyzed by Human CYP3A4", J. Chem. Inform. Model. 2023, 63, 7826–7836. https://pubs.acs.org/doi/abs/10.1021/acs.jcim.3c01630 (3)      Hajime Hirao and Enhua Zhang, "Bidirectional Charge Transfer at the Heme Iron in Reversible and Quasi-Irreversible Cytochrome P450 Inhibition", Inorg. Chem. 2023, 52, 16599–16608. https://pubs.acs.org/doi/abs/10.1021/acs.inorgchem.3c02541

Hajime Hirao is a Professor at the School of Medicine at the Chinese University of Hong Kong, Shenzhen. He received his bachelor's degree and master's degree from Kyoto University in 1998 and 2000, respectively, and earned his PhD from the University of Tokyo in 2004. He has published over 175 papers in international journals.