Physical Chemistry Seminar: "Protein Dynamics and the Evolution of Antibiotic Resistance"


4 to 5 p.m., April 15, 2024


Clara Frost
Graduate Student, Chemistry and Biochemistry, The University of Arizona


The presence of rapid dynamics, or lack thereof, in laboratory evolved enzymes has furthered our understanding of the components necessary to design an artificial enzyme. In this study, we turn towards ancestral enzymes to uncover changes in these components throughout natural evolution. Beta lactamases have existed for billions of years, and remain one of the primary enzymes responsible for antibiotic resistance. From previous applications of sequential reconstruction on these ancestral enzymes, we are able to study the crystal structure of a laboratory resurrected gram-negative bacteria Beta lactamase (GNCA). The structural changes are minor compared to its modern counterpart, a class A TEM-1 Beta lactamase, implying that dynamic effects play an important role in the evolution of its function and specificity. We employed Transition Path Sampling on both the modern and ancestral Beta lactamases, and found that the extant species contains rapid dynamics in the active site that are missing in the ancestral enzyme. Uncovering these evolutionary required changes are proving to be essential if we hope to synthesize enzymes that can compete with the catalytic rates of natural enzymes. 


I'm from Falls Church City, VA and came to the UofA after graduating from the College of William & Mary in 2020. Now I'm a 4th year PhD candidate in Dr. Schwartz's group, where we use computational methods to study the atomic details of enzymatic catalysis.