Chemical Society Seminar: - Peter Wolynes: Protein Dynamics and the Brain
The brain is a molecular computer. How the brain computes, and feels and learns and remembers remain great mysteries. Neurobiologists have, however, identified some key protein actors in the mechanisms of learning and memory. I will describe some theoretical and computational efforts in understanding some of the molecular aspects of 1) Hebbian learning through the regulatable assembly of the actin cytoskeleton in dendritic spines, 2) the hypothesis that long-term memory involves a functional prion protein and 3) some aspects of the physical chemistry of aggregation processes that are involved in the pathogenesis of Huntington’s disease and Alzheimer’s disease.
Peter G. Wolynes was born in Chicago, Illinois in 1953. He completed his undergraduate studies at Indiana University, receiving an A.B. degree in 1971. He then took up the study of statistical mechanics at Harvard University, where he received his Ph.D. in chemical physics in 1976. After a brief postdoctoral study with John Deutch at MIT, Wolynes returned to Harvard as an assistant professor in 1976. During the next four years at Harvard, Wolynes worked on the dynamical theory of electrolyte solutions, as well as on the then-nascent theoretical study of molecular dynamics of proteins. His early work on the theory of chemical reaction rates in condensed phases paved the way for the explosion of theoretical developments in this area throughout the 1980’s. In 1980, Wolynes moved to the University of Illinois, Urbana-Champaign, where he progressed to be the Eiszner Professor of Chemistry and a Center for Advanced Study Professor of Chemistry, Physics and Biophysics. During the years he spent at Illinois, Wolynes worked on a wide range of theoretical problems in chemical physics, including the theory of the glass transition (now called the Random First Order Transition theory) and the development of new techniques for studying quantum dynamics in condensed phases based on path integrals. He developed, in 1981, the quantum mechanical version of Kramers' celebrated 1940 theory of chemical reaction rates in solution. He later extended these ideas to study nonadiabatic reactions, such as biological electron transfer. In addition, Wolynes provided a new picture of how energy flows quantum mechanically in moderate-sized molecules through a network of Fermi resonances. Wolynes's interest in applying statistical mechanics to biology grew while he was at Illinois. He introduced energy landscape ideas to the field of protein folding, providing a statistical mechanical framework to understand how a one-dimensional sequence of amino acids folds to its native structure on a biologically relevant timescale. These ideas have led to what has been termed the "New View" of protein folding kinetics. Energy landscapes have also proved useful in developing algorithms to predict protein structure from sequence and are the basis for recent advances in protein structure prediction. Wolynes's scientific contributions have been acknowledged in many ways. He received from the ACS, its Award in Pure Chemistry in 1986, the Fresenius Award in 1988, the Peter Debye Award for Physical Chemistry in 2000 and its Award in Theoretical Chemistry in 2012. He received the Biological Physics Prize of the American Physical Society in 2004 (now called the Delbrück prize) and the Founders Award from the Biophysical Society (2008). Among other external appointments, he has been the Hinshelwood lecturer at Oxford in 1997, Linnett Professor at Cambridge in 2011, and Fogarty Scholar-in-Residence at the National Institutes of Health starting in 1994. He was elected in 1991 to the National Academy of Sciences and the American Academy of Arts & Sciences. Wolynes was elected to the American Philosophical Society (2006), the German Academy of Sciences, “LeopoIdina” (2007) and as a Foreign Member to the Royal Society (2007) and the Indian National Science Academy (2016). In 2000, Wolynes moved to University of California, San Diego, where he held the Francis Crick Chair in the Physical Sciences. In addition to continuing his work on many body chemical physics and protein folding, he is now using energy landscape ideas to explore problems in cell biology ranging from chromosome dynamics to the mechanism of long-term memory. In 2011, Wolynes moved to Rice University in Houston, Texas where he is the D.R. Bullard-Welch Foundation Professor of Science. He was named Co-Director of the NSF Center for Theoretical Biological Physics at Rice University in 2019.