Biography

Dorothee Kern is Professor of Biochemistry at Brandeis University and an Investigator of the Howard Hughes Medical Institute. She received her PhD at the Martin Luther University in Halle, Germany and then carried out her postdoctoral studies at UC Berkeley. She joined the faculty at Brandeis University in 1999.

Dr. Kern's research group studies the dynamical nature of proteins with the goal to reveal the interplay between structure, dynamics and function. Kern has been a major contributor in the experimental characterization of protein dynamics during enzyme catalysis and signaling.

Dr. Kern is the recipient of the Pfizer Award in Enzyme Chemistry from the American Chemical Society, the Dayhoff Award from the Biophysical Society, the Young Investigator Award of the International Association for Protein Structure Analysis and Proteomics and the Strage Award for Aspiring Young Science Faculty. Before her professional scientific carrier, she was captain of the German National Basketball team for many years and won the MVP award.

 

Dorothee Kern, Ph.D.

Professor of Biochemistry
Howard Hughes Medical Institute, Brandeis University

www.bio.brandeis.edu/faculty/kern.html

Dynamic Personalities of Proteins

Abstract:
The synergy between structure and dynamics is essential to the function of biological macromolecules. While this is a widely accepted concept, key questions remain: Have proteins evolved so that substates necessary for activity are preferable accessible? How do motions on different timescales relate to each other and contribute to biological function?

The lecture will address these questions. First, we show experimentally that motions in enzymes are not random but preferentially follow the pathways, which create the configuration capable of proficient chemistry. This situation is analogous to protein folding, which is biased so as to sample only a small portion of the energy landscape. The expansion of the concept of non-random sampling of conformational space for efficient biological function from folding to conformational rearrangements within the folded space combines both phenomena through the energy landscape. The timescale and amplitude of motion were characterized by a combination of NMR relaxation, x-ray, single molecule FRET experiments and molecular dynamics simulations. The determined predisposition of enzymes to move in the direction utilized for catalysis may be a key factor for the efficiency of biocatalysts.

Second, the hierarchy in space and time for proteins is discussed. The linkage between three different “tiers” of dynamic timescales: (i) Thermally driven, fast (ps), local atomic fluctuations, (ii) faster (ns) motions of whole segments and (iii) larger amplitude, collective, slower motions ( ms-ms), the time-scale of catalysis is characterized. Besides this linkage, a direct connection from those dynamic features to function and stability is made.