Research

Our current research is primarily focused on constructing sequence-structure-function relationships through computational methods (atomistic simulation and molecular phylogenetics)

Flavin-dependent Hydroxylases: The study of these enzymes has a long University of Michigan history starting with Prof. Vincent Massey continuing with Profs. David Ballou and Bruce Palfey specifically focusing on bacterial para-hydroxy-benzoate hydroxylase (PHBH). They made significant contributions to understanding the catalytic cycle of PHBH as well as the role that flavin dynamics plays in the hydride transfer step. Now in collaboration with the labs of Profs. Alison Narayan and Janet Smith, we are studying the distantly related fungal flavin-dependent hydroxylases (SorbC/TropB/AfoD/AzaH). Our approach involves both molecular modeling and ancestral sequence reconstruction to construct complex models of substrate binding and the energy landscape for catalytic steps that can then be tested in the lab. Understanding how specific functions evolved from a common ancestor will enable the redesign of these enzymes to carry out difficult synthetic tasks.