NMR at its best - evolution of protein dynamics over 3.5 billion years and new strategies for drug design
Dorothee Kern, HHMI/ Brandeis University, Dept. of Biochemistry, Waltham, USA
As a direct manifestation of molecular kinetic energy, temperature is a fundamental evolutionary driver for chemical reactions. However, it is currently not understood how the natural evolution of catalytic efficiency responds to dramatic changes in environmental temperatures. Using Ancestral Sequence Reconstruction (ASR) we resurrect and biophysically characterize the oldest common ancestral kinase and enzymes along the evolutionary path to modern kinases. Strikingly, enzymes coped with an inherent drop in catalytic speed caused as the earth cooled down over 3.5 billion years by accelerating protein dynamics and adapting thermostability by unexpected mechanisms, as characterized by NMR. (1). In the second part of my talk I discuss novel and unconventional ideas for rational drug design based on protein dynamics.
(1) V. Nguyen, C. Wilson, M. Hoemberger, J. Stiller, R. Agafonov, J. English, S. Kutter, D. Theobald and D. Kern “Evolutionary Drivers of Thermoadaptation in Enzyme Catalysis” Science 2017
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. Her research group studies the dynamical nature of proteins with the goal to reveal the interplay between structure, dynamics and function. She has been a major contributor in the experimental characterization of protein dynamics during enzyme catalysis and signaling. She pursues a new vision of protein dynamcis and allosteric networks at the heart of drug discovery. Recently Dr. Kern is reconstructing the evolution of proteins over billions of years. Dr. Kern is the recipient of the Pfizer Award in Enzyme Chemistry from the American Chemical Society, the National Lecturer of the Biophysical 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 an MVP award.