High-valent Protein Engeineering

Keywords: QM/MM, TeraChem, Amber, DFT

The overarching direction of my thesis is to elucidate patterns governing substrate-protein relationships in high-valent enzymes. More specifically, I am interested in how the protein environment influences reactivity and substrate specificity in non-heme iron containing enzymes. As it currently stands, my research spans three general areas of interest. 1) Elucidating the role of the active site and greater protein environment in mediating hydroxylase vs. halogenase reactivity in non-heme iron dioxygenases. 2) Investigating the role of electronic allostery, charge transfer, and electronic perturbations in mediating reactivity in iron-containing enzymes. 3) Leveraging modern machine learning techniques to identify patterns in complex MD or multiscale QM/MM simulations.

Related Publications:

Flores, A.D; Kastner, D.W.; Du, Y.; Narayanamoorthy, M.; Shen, Y.; Cai, W.; Vennelakanti, V.; Zill, A.A.; Dell, L.B.; Zhai, R; Kulik, H.J.; Zhang, W.; “Probing the mechanism of isonitrile formation by a non-heme iron(II)-dependent oxidase/decarboxylase” Journal of the American Chemical Society. 144(13), 5893-5901 2022.

Nazemi, A.; Steeves, A.H.; Kastner, D.W.; Kulik, H.J.; “Influence of the Greater Protein Environment on the Electrostatic Potential in Metalloenzyme Active Sites: The Case of Formate Dehydrogenase” Journal of the American Chemical Society. 126(22), 2069-4079 2022.