Prof. Hajime HIRAO published an article on P450-mediated drug metabolism in the Journal of American Chemical Society
Recently, Professor Hajime HIRAO from the Warshel Institute for Computational Biology, School of MEDICINE, The Chinese University of Hong Kong, Shenzhen, along with his team (Ms. Dongxiao YUE, a Ph.D. student, and Dr. Elvis Wang Hei NG, currently at the Department of Pharmacology and Pharmacy, The University of Hong Kong), published a paper titled “Hydrogen-Bond-Assisted Catalysis: Hydroxylation of Paclitaxel by Human CYP2C8” in the Journal of the American Chemical Society.
The first author of the paper is Dongxiao YUE, a Year 2021 Ph.D. student in Biological Sciences, School of MEDICINE, The Chinese University of Hong Kong, Shenzhen. Professor Hajime HIRAO is the corresponding author of this paper.
Drug metabolism by human cytochrome P450 enzymes (P450s) is well-established, yet the microscopic mechanisms underlying P450-mediated metabolism are not fully understood. This is partly due to the large and flexible active sites of human P450s and the intricate chemical structures of drug compounds. Moreover, limited structural data on P450–drug complexes presents additional challenges. Prof. HIRAO’s team addressed these complexities using advanced computational chemistry techniques, including the hybrid quantum mechanics/molecular mechanics (QM/MM) approach. They focused on the CYP2C8-catalyzed hydroxylation of paclitaxel (also known commercially as Taxol), a natural-product anticancer drug with a notably complex structure. Their study revealed unique reactivity patterns that diverge from those seen in typical P450-catalyzed reactions. This pioneering work lays a foundation for further computational investigations into P450-mediated drug metabolism and is expected to enhance the precision of drug discovery processes by offering detailed mechanistic insights into the metabolic profiles of drug compounds.
Link to the article: https://pubs.acs.org/doi/full/10.1021/jacs.4c07937
The team gratefully acknowledges support from the Ganghong Young Scholar Development Fund, the Changjiang Scholarship, the Guangdong Pearl River Talent Program, the Shenzhen Natural Science Foundation 2022 fund, and funding for the Warshel Institute for Computational Biology provided by Shenzhen City and Longgang District.
Professor Hajime HIRAO
Presidential Fellow
World's Top 2% Scientist
Professor Hajime HIRAO earned his Bachelor’s and Master’s degrees from Kyoto University in 1998 and 2000, respectively, and his Ph.D. from the University of Tokyo in 2004. He conducted postdoctoral research at the Hebrew University of Jerusalem, Emory University, and Kyoto University. Over his career, he has been involved in computational chemistry research at institutions such as Novartis, Nanyang Technological University, and City University of Hong Kong. His research group focuses on using computational methods to uncover the fundamental principles of chemical reactions and molecular interactions in both natural and laboratory settings, with a particular interest in the chemistry and pharmacology of cytochrome P450 enzymes.
