5/17 – Yihan Shao, University of Oklahoma

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Speaker: Yihan Shao, PhD

Assistant Professor, Department of Chemistry and Biochemistry, University of Oklahoma

Title: Towards Affordable Free Energy Simulation of Enzyme Reactions

Abstract:  To help unravel enzyme reaction mechanisms and assist enzyme engineering, it is desirable to computationally model the free energy profile of enzyme reactions.  But such modeling is notoriously expensive, which can take 100,000-1,000,000 CPU hours for each enzyme.  This high cost arises from the need to perform combined quantum mechanical molecular mechanical (QM/MM) calculations for millions of enzyme configurations to capture the bond breaking/formation process.  We will introduce two approaches to accelerate these free energy simulations, so that they become more affordable.  In the first approach, we constructed the first machine-learning potential for accurately predicting energy and forces of enzyme configurations (J. Chem. Theory Comput. 2021, 17, 5745).   In the second approach, we combined an improved semi-empirical QM/MM model and an ab initio QM/MM model in multiple-time-step simulations (10.26434/chemrxiv-2022-0zg7j).  The efficiency and accuracy of these approaches will be demonstrated with applications to the chorismate mutase reaction.