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Understanding Metalloenzyme Catalysis with QM/MM Free Energy Simulations

By Qiang Cui
Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin-Madison

I’ll discuss challenges associated with understanding enzyme catalysis using hybrid QM/MM simulations, especially metalloenzymes that feature a dynamic active site and/or a high degree of solvent accessibility. Relevant examples include molecular motors, DNA repair enzymes and enzymes with a high degree of catalytic promiscuity. I’ll discuss recent developments in the density functional tight binding (DFTB) model and its integration with efficient sampling techniques (e.g., the thermal string approach) as well as with high-level QM/MM methods for more quantitative free energy computations. The developments are illustrated with several recent applications.