Dr. Heidi Klem
Louisiana State University
Friday, October 9, 2026
12:00 Noon
Meyerhoff Chemistry BuildingRoom 120
Host: Dr. Joe Bennett
Modeling the Enzyme Active Site: A Moving Target in Mechanistic Chemistry
The term enzyme active site is familiar to anyone who has taken a biochemistry course, yet it evades a universal compositional definition. This ambiguity highlights a considerable challenge in quantum mechanical (QM) studies of enzyme reactions, where the catalytic region must be explicitly defined. Construction of these enzyme models relies on many user decisions beyond region selection as well, including how to represent the surrounding environment, and what conformations are relevant. These choices can strongly influence the reliability of the model and, consequently, the mechanistic insight. In this talk, I will discuss how this challenge motivated the development of QMzyme, a Python package designed to support systematic and reproducible construction of quantum mechanical (QM)-based enzyme models. I will reflect on completed and ongoing studies that illustrate the active site as a moving target, physically and figuratively, including allosteric conformational change in imidazole glycerol phosphate synthase, counterintuitive enzyme activity that dictates phenotypic differences in the Great Blue and White Herons, and the interplay between substrate positioning and beta-lactamase electric field that may inform inhibitor design.