Department of Chemistry and Biochemistry
Physical Chemistry Seminar Series

Anastassia Alexandrova, UCLA
May 13, 2024
2:00pm in Tykeson 140
Hosted by: Alexander Batelaan

Enzymes as Molecular Capacitors

Proteins have been shown to produce intramolecular electric fields, preorganized to help enzymatic catalysis. Using IR probes placed in proteins, and measuring their Stark shift, it became possible to assess the local fields at the location of the probe, and correlate those with the reactivity. The talk will show that in fact, 3-D fields in the entirety of the active site (as opposed to a particular bond) are relevant to catalysis.

I will show that the diverging reactivity of the natural Fe-heme proteins is strongly regulated by the electric field from the protein, outside of the primary coordination sphere of the Fe. Next, I will use Protoglobin as a model, which was evolved to efficiently catalyze carbene transfer reactions, to show that what directed evolution developed is a highly strategic electric field that facilitates the reaction. The field is strongly heterogeneous and curvy, aligned opposite to the direction of the electron flow in the reaction. I will demonstrate that electric fields are dynamic. Each protein can visit several characteristic fields, only some of which are strongly catalytic, and some may promote different reaction mechanisms.

The talk will highlight several methods for field analysis, directly as a vector object, and indirectly via the scalar field of electronic charge density. These ideas and methods pertain to our understanding f how enzymes work, how they evolve toward acquiring a function, and how they should be designed to be competitive with natural enzymes.