报告题目：Dynamics and Reaction Mechanism of Phosphate Catalytic Enzymes

报 告 人 ：Prof. Edina Rosta

报告时间：2018年7月10日（周二）上午10:00

报告地点：东三楼321会议室

邀 请 人 ：廖荣臻教授

报告人简介：

Prof. Edina Rosta obtained her Chemistry PhD in 2007 from University of Southern California, Los Angeles, CA, under the supervision of Prof. Arieh Warshel, who won the 2013 Nobel Prize in Chemistry. Then, she worked as a postdoctoral research fellow in National Institutes of Health during 2007-2012. She started her independent research group at King's College London in 2012. She has published many papers in international journals, including Nature, Proc. Natl. Acad. Sci. U.S.A., J. Am. Chem. Soc, Angewandte Chemie and Phys. Rev. X. Among the awards and honors she received, she won NIH Fellows Award for Research Excellence (2012), NIH Fellows Award for Research Excellence (2011), Nancy Nossal Fellowship Award of NIH. She is an association editor of Frontiers in Biological Modeling and Simulations.

报告摘要：

The formation and cleavage of phosphate bonds is essential in most biological processes including nucleic acid processing. Many enzymes that catalyze phosphate hydrolysis require bound Mg²⁺ ions. Here, we focus on two such enzymes that carry out NTP cleavage: dUTPases and RAF kinases. We present atomistic molecular dynamics simulation results, a novel Markov model-based kinetic analysis, and experimental mutational studies providing structural insights for the RAF activation mechanism. Our results offer new prospective pathways in rational drug design for overcoming dimerization-related drug resistance.