104 Gore Hall, Newark, DE, 19716


Wednesday, November 15, 2017 - 15:45 to 16:45
The origin of the remarkable rate acceleration exhibited by enzymes is a
topic of longstanding debate and many ideas have been proposed.
Electrostatic interactions impact every aspect of the structure and function
of proteins, nucleic acids, and membranes. The transition states for many
enzyme-catalyzed reactions involve a change in the distribution of charge
relative to the starting material and/or products, and the selective
stabilization of charge-separated transition states may be essential for
catalysis. The magnitudes of the electric fields in proteins and the
variations in these fields at different sites are predicted to be enormous,
but it is a challenge to obtain quantitative experimental information on
these fields. We have developed the vibrational Stark effectto probe
electrostatics and dynamics in organized systems, in particular in proteins
where they can report on functionally important electric fields. The
strategy involves deploying site-specific vibrational probes whose
sensitivity to an electric field is measured in a calibrated external electric
field. Once calibrated, these probes, typically nitriles or carbonyls, can be
used to probe changesin electric field due to mutations, ligand binding, pH
effects, light-induced structural changes, etc. We can also obtain
information on absolutefields by combining vibrational
solvatochromismand MD simulations, checked by the vibrational Stark
effect calibration.